11 7

Proje Grubu: KBAG Sayfa Sayısı: 102 Proje No: 117Z735 Proje Bitiş Tarihi: 15.04.2019 Metin Dili: Türkçe İndeks Tarihi: 08-11-2020

MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması

Öz:
Projede, MCF-7 meme kanser hücrelerinde, glukoz ve oksijen yokluğunda Warburg fenomeni ve Crabtree etkisinin glikolizin metabolik kontrol enzimlerinin gen ekspresyonu düzeyinde araştırılması amaçlandı. Kanser hücreleri proliferasyon üzerine kurulmuş normal hücrelerden farklı bir metabolizma gösterir. Normal hücrelere göre, kandan glukozu 5-10 kat daha fazla aldığı, oksijen varlığından bağımsız aerobik şartlar altında laktik asit üreten glikolitik yolu tercih ettiği ileri sürülmektedir. Kanser hücre metabolizması ile normal hücre metabolizması arasındaki bu fark Warburg fenomeni olarak adlandırılır. Metabolik enzimler, kanser hücresinin büyümesinde önemli düzenleyicidir. Hipoksi, kanser gelişiminde çok yönlü rolüyle uzun zamandır bilinmektedir ve katı tümörlerin en önemli özelliklerinden biri olarak kabul edilmektedir. Dolayısı ile kanser hücresinde karbonhidrat metabolizmasının iki temel özelliği hipoksi ve hipoglisemidir. Planlanan çalışmada kanser hücresinin iki temel özelliği birlikte değerlendirildi. Bu amaçla, MCF-7 hücreleri, 0; 5,5; 15 ve 55 mM glikoz konsantrasyonları içeren mediumlarda 3, 6, 12 ve 24 saat normoksi (% 20 O2) ve hipoksi (%1O2) koşullarına maruz bırakıldı. Uygulama koşullarının hücre proliferasyonu üzerine etkileri WST-1 canlılık testi ile belirlendi. Deneme sonunda hücrelerden izole RNA?larda, hekzokinaz 2, piruvat kinaz M2, glukoz 6 fosfat dehidrogenaz, laktat dehidrogenaz A, fosfofruktokinaz1, gliseraldehit 3 fosfat dehidrogenaz enzimlerinin gen ekspresyonları ile HIF? ve GLUT1 genlerinin ekspresyon düzeyleri RT-PCR?da Syber green yöntemi ile kantitatif olarak belirlendi. Hücrelerin mikro çevresindeki glukoz ve laktik asit miktarları kolorimetrik olarak tayin edildi. Çalışmanın laktat sonuçları, MCF 7 hücrelerinde Crabtree etkisinin baskın olduğunu gösterdi. Glikoliz enzimleri ve G6PD enziminin mRNA ifadeleri değerlendirildiğinde, aerobik glikoliz akışının aktif olduğu; kanser hücresinin çoğalması sırasında ihtiyaç duyulan biyomoleküllerin sentezi için gerekli olan pentoz fosfat yolunun, yüksek glukoz ve hipoksik ortamda aerobik glikolizden daha etkin rol oynadığı sonucuna varıldı.
Anahtar Kelime: gen ekspresyonu aerobik glikoliz glut1 hıf? hipoksi anahtar kelimeler: mcf7

Erişim Türü: Erişime Açık
  • Adamaki, M., Georgountzou, A., Moschovi, M. 2012.“Cancer and the Cellular Response to Hypoxia”, Pediatr Therapeut, 3(2),1-21.
  • Adewale, F., Basiru, A., Oluwafemi, O., Olusola, A., Israel, O., Rosemary, E., 2017. “Biology of glucose metabolization in cancer cells”, Journal of Oncological Sciences, 3(2), 45-51.
  • Airley, R., Loncaster, J., Davidson, S., Bromley, M., Roberts, S., Patterson, A., Hunter, R., Stratford, I., West, C. 2001. “Glucose transporter GLUT-1 expression correlates with tumor hypoxia and predicts metastasis free survival in advanced carcinoma of the cervix”, Cancer Res., 7, 928–934.
  • Barar, J., Omidi, Y. 2013. “Dysregulated pH in tumor microenvironment checkmates cancer therapy”, BioImpacts.3(4),149-162.
  • Batetta, B., Pani, A., Putzolu, M., Sanna, F., Bonatesta, R., Piras, S., Spano, O., Mulas, M.F., Dessi, S. 1999. “Correlation between cholesterol esterification, MDR1 gene expression and rate of cell proliferation in CEM and MOLT4 cell lines”, Cell Prolif, 32, 49–61.
  • Baysal, B.E., Ferrell, R.E., Willett-Brozick, J.E., Lawrence, E.C., Myssiorek, D., Bosch, A., van der Mey, A., Taschner, P.E., Rubinstein, W.S., Myers, E.N., Richard ,C.W. , Cornelisse, C.J., Devilee, P., Devlin, B. 2000. “Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma”, Science, 287(5454), 848–851.
  • Bensinger, S. J., Christofk, H. R. 2012. "New aspects of the Warburg effect in cancer cell biology", Seminars in Cell and Developmental Biology, 23(4), 352–361.
  • Bluemlein, K., Grüning, N.M., Feichtinger, R.G., Lehrach, H., Kofler, B., Ralser, M. 2011. “No evidence for a shift in pyruvate kinase PKM1 to PKM2 expression during tumorigenesis”, Oncotarget, 2, 393–400.
  • Brown, R.S., Goodman, T.M., Zasadny, K.R., Greenson, J.K., Wahl, R.L. 2002. “Expression of hexokinase II and GLUT-1 in untreated human breast cancer”, Nucl. Med. Biol. 29, 443– 453.
  • Brown, R.S., Wahl, R.L. 1993. “Overexpression of GLUT-1 glucose transporter in human breast cancer”, Cancer 72, 2979–2985.
  • Buchakjian, M.R., Kornbluth, S. 2010. “The engine driving the ship: Metabolic steering of cell proliferation and death”, Nature Reviews Molecular Cell Biology, 11(10), 715–727.
  • Burgman, P., Odonoghue, J.A., Humm, J.L., Ling, C.C. 2001. “Hypoxia-Induced increase in FDG uptake in MCF7 cells”. J Nucl Med 42(1):170–175.
  • Cairns, R. A, Harris, I., McCracken, S., Mak, T. W. 2011. "Cancer cell metabolism", Cold Spring Harbor Symposia on Quantitative Biology, 76, 299–311.
  • Calcinotto, A., Filipazzi, P., Grioni, M., Iero, M., De Milito, A. vd. 2012. “Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes”, Cancer Res. Jun 1, 72(11), 2746-56.
  • Carvalho, K.C., Cunha, I.W., Rocha, R.M., Ayala, F.A., Cajaíba, M.M., Begnami, M.D., Vilela, R.S., Paiva, G.R., Andrade, R.G., Soares, F.A. 2011. “GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker”, Clinics, 66,965–972.
  • Cengiz, M., Boyunağa, H., Yildiz, F. Ural, U.A., Atahan, İ.L. 2006. “Alteration of Tumor Glucose Metabolism after Radiotherapy in MCF-7 Breast Cancer Cell Lines”, International Journal of Hematology and Oncology, 16,4, 172–77.
  • Chaneton, B., Gottlieb, E. 2012. “PGAMgnam style: A glycolytic switch controls bio synthesis”, Cancer Cell, 22(5), 565–566.
  • Chang, C.H., Curtis, J.D., Maggi, Jr L.B., vd. 2013. “Posttranscriptional control of T cell effector function by aerobic glycolysis”, Cell, Jun 6,153(6),1239-1251.
  • Chen, C., Pore, N., Behrooz, A., Ismail-Beigi, F., Maity, A. 2001. “Regulation of GLUT1 mRNAby hypoxia-inducible factor-1. Interaction between H-ras and hypoxia”, J Biol Chem, 276(12), 9519–9525.
  • Colell, A., Green, D.R., Ricci, J.E. 2009. “Novel roles for GAPDH in cell death and carcinogenesis”, Cell Death Differ,16:1573-1581.
  • Compagno, M., Lim, W.K., Grunn, A., Nandula, S.V., Brahmachary, M., Shen, Q., Bertoni, F., Ponzoni, M., Scandurra, M., Califano, A. vd. 2009. “Mutations of multiple genes cause deregulation of NFkappaB in diffuse large B-cell lymphoma”, Nature, 459,717–721.
  • Covian, R., Moreno-Sanchez, R. 2001. “Role of protonatable groups of bovine heart bc(1) complex in ubiquinol binding and oxidation”, Eur J Biochem 268, 5783–5790
  • Dehne, N., Hintereder, G., Brüne, B. 2010. "High glucose concentrations attenuate hypoxiainducible factor-1α expression and signaling in non-tumor cells", Experimental Cell Research, 316(7), 1179–1189.
  • Duckwall, C. S., Athanasaw, M.T., Young, J.D. 2013. “Mapping Cancer Cell Metabolism with 13 C Flux Analysis: Recent Progress and Future Challenges”, Journal of Carcinogenesis, 12 (13), 1–7.
  • Erdamar, H., Hacıevliyagil Kazancı F., Gök, S. 2015. “Biochemical Changes in Cancer Kanserde Biyokimyasal Değişiklikler”, Journal of Clinical and Analytical Medicine, 1–9. doi:10.4328/JCAM.3234.
  • Fang, Z., Jiang, C., Feng,Y., Chen, R., Lin, X., Zhang, Z., Han, L., Chen, X., Li, H., Guo, Y., Jiang, W. 2016. "Effects of G6PD activity inhibition on the viability, ROS generation and mechanical properties of cervical cancer cells" Biochimica et Biophysica Acta 1863 (9), 2245- 2254.
  • Fang, M., Shen, Z., Huang, S., Zhao, L., Chen, S., Mak, T.W., Wang, X. 2010. “The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway”, Cell 143, 711–724.
  • Feng, C., Gao, Y., Wang, C., Yu, X., Zhang, W., Guan, H.,Shan, Z., Teng, W. 2013. “Aberrant Overexpression of Pyruvate Kinase M2 Is Associated With Aggressive Tumor Features and theBRAFMutation in Papillary Thyroid Cancer”. The Journal of Clinical Endocrinology & Metabolism, 98(9), E1524–E1533.
  • Gao, L., Mejías, R., Echevarría, M., & López-Barneo, J. 2004. “Induction of the glucose-6- phosphate dehydrogenase gene expression by chronic hypoxia in PC12 cells”, FEBS Letters, 569(1–3), 256–260.
  • Gillies, R.J., Robey, I., Gatenby, R.A. 2008. “Causes and consequences of increased glucose metabolism of cancers”, J Nucl Med, 49 Suppl 2(6), 24S-42S.
  • Gordan, J.D., Simon, C.M. 2007. “Hypoxia-Inducible Factors: Central Regulators of the Tumor Phenotype”, Current Opinion in Genetics and Development, 17 (1), 71–77.
  • Guillaumond, F., Leca, J., Olivares, O., Lavaut, M.-N., Vidal, N., Berthezene, P., Vasseur, S. 2013. Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proceedings of the National Academy of Sciences, 110(10), 3919–3924.
  • Guo, C., Liu, S., Sun, M.Z. 2013. “Novel insight into the role of GAPDH playing in tumor”, Clin Transl Oncol,15:167-172.
  • Guppy, M., Leedman, P., Zu, X., Russell, V. 2002. “Contribution by different fuels and metabolic pathways to the total ATP turnover of proliferating MCF-7 breast cancer cells”, Biochem. J., 364 309–315.
  • Hamdan, F.H., Zihlif, M.A. 2014. “Gene expression alterations in chronic hypoxic MCF7 breast cancer cell line”, Genomics, 104(6), 477–481.
  • Han, L., Ma, Q., Li, J., Liu, H., Li, W., Ma, G., Xu, Q., Zhou, S., Wu, E. 2011. "High Glucose Promotes Pancreatic Cancer Cell Proliferation via the Induction of EGF Expression and Transactivation of EGFR" PLOS ONE, 6 (11): e27074.
  • Han, J., Zhang, L., Guo, H., Wysham, W. Z., Roque, D. R., Willson, A. K. vd. 2015. “Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling”, Gynecologic Oncology, 138(3), 668–675.
  • Hashimoto, T., Hussien, R., Oommen, S., Gohil, K., Brooks, G.A. 2007. “Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis”, FASEB J, 21: 2602-12.
  • Higashi, K., Ueda, Y., Sakurai, A., Mingwang, X., Xu, L., Murakami, M. vd. 2000. “Correlation of GLUT-1 Glucose Transporter Expression With [(18)F]FDG uptake in non-small cell lung cancer” European Journal of Nuclear Medicine, Vol. 27, No. 12, 1778-1785.
  • Hitosugi, T., Zhou, L., Elf, S., Fan, J., Kang, H. B., Seo, J. H., vd. 2012. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell, 22(5), 585–600.
  • Hu, C.J., Wang, L.Y., Chodosh, L.A., Keith, B., Simon, M.C. (2003). "Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2 alpha in hypoxic gene regulation." Molecular and Cellular Biology, 23 (24), 9361–9374.
  • Hou, Y., Zhou, M., Xie, J., Chao, P., Feng, Q., Wu, J. 2017. " High glucose levels promote the proliferation of breast cancer cells through GTPases", Dove Medical Press, 9, 429–436.
  • Ishiyama, M., Tominaga, H., Shiga, M., Sasamoto, K., Ohkura, Y., Ueno, K. 1996. " A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet. " Biological and Pharmaceutical Bulletin, 19 (11), 1518- 1520.
  • Israelsen, W.J., Dayton, T.L., Davidson, S.M., Fiske, B.P., Hosios, A.M., Bellinger, G., vd. 2013. “PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells”, Cell, 155(2), 397–409.
  • Ito, S., Fukusato, T., Nemoto, T., Sekihara, H., Seyama, Y., Kubota, S. 2002. “Coexpression of glucose transporter 1 and matrix metalloproteinase-2 in human cancers”, J Natl Cancer Inst, 94(14),1080–1091.
  • Iyer, N.V. Kotch, L.E., Agani, F., Leung ,S.W., Laughner, E., Wenger, R.H., Gassmann, M., Gearhart, J.D., Lawler, A.M., Yu, A.Y., Semenza, GçL. 1998. “Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha”, Genes Dev. 12, 149–162.
  • Iyer, V.V., Yang, H., Ierapetritou, M.G., Roth, C.M. 2010. “Effects of glucose and insulin on HepG2-C3A cell metabolism”, Biotechnology and Bioengineering, 107(2), 347–356.
  • Ji, H, Ramsey, M.R., Hayes, D.N., Fan, C., McNamara, K. vd. 2007. “LKB1 modulates lung cancer differentiation and metastasis”, Nature, 448, 807–10
  • Jiang, B. 2017. “”Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment”, Genes and Diseases, 4(1), 25–27.
  • Jiang, P., Du, W., Wu, M. 2014. “Regulation of the pentose phosphate pathway in cancer”, Protein and Cell, 5(8), 1–11.
  • Jiang, P., Du, W., Yang, X. 2013. “A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation”, Cell Cycle, 12, 3720–3726.
  • Johnson, R.F., Perkins, N.D. 2012. “Nuclear factor-kappaB, p53, and mitochondria: regulation of cellular metabolism and the Warburg effect”, Trends Biochem Sci, 37, 317–24.
  • Kalyanaraman, B. 2017. “Teaching the basics of cancer metabolism: Developing antitumor strategies by exploiting the differences between normal and cancer cell metabolism”, Redox Biology, 12(April), 833–842.
  • Kennedy, K. M., Dewhirst, M.W. 2010. “Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation”, Future Oncology, 6(1), 127–148.
  • Koppenol, W.H., Bounds, P.L., Dang, C.V. 2011. “Otto Warburg’s contributions to current concepts of cancer metabolism”, Nat. Rev. Cancer 11 (5), 325–337.
  • Koshiji, M., Kageyama, Y., Pete, E.A., Horikawa, I., Barrett, J.C., Huang, L.E. 2004. "HIF-1 alpha induces cell cycle arrest by functionally counteracting Myc."The EMBO Journal, 23(9), 1949–1956.
  • Koukourakis, M.I., Giatromanolaki, A., Simopoulos, C., Polychronidis, A., Sivridis, E.E. 2005. “Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis”, Clin. Exp. Metastasis, 22, 25–30.
  • Kroemer, G., Pouyssegur, J. 2008. “Tumor Cell Metabolism: Cancer’s Achilles’ Heel”, Cancer Cell, 13(6), 472–482.
  • Kruger, A., Gruning, N. M., Wamelink, M. M., Kerick, M., Kirpy, A., Parkhomchuk, D., et al. (2011). The pentose phosphate pathway is a metabolic redox sensor and regulates transcription during the antioxidant response. Antioxidants & Redox Signaling, 15(2), 311–324.
  • Krzeslak, A., Wojcik-Krowiranda, K., Forma, E., Jozwiak, P., Romanowicz, H., Bienkiewicz, A., Brys, M. 2012. “Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers”, Pathology and Oncology Research, 18(3), 721–728.
  • Kumar, V.B., Viji, R.I., Kiran, M.S., Sudhakaran, P.R. 2007. “Endothelial cell response to lactate: implication of PAR modification of VEGF”, J Cell Physiol, May 211(2), 477-485.
  • Kwon, S. J., & Lee, Y. J. 2005. “Human Cancer Biology Effect of Low GLUTamine / Glucose on Hypoxia-Induced Elevation of Hypoxia-Inducible Factor-1A in Human Pancreatic Cancer MiaPaCa-2 and Human Prostatic Cancer DU-145 Cells”. Clinical Cancer Research, 11(13), 4694–4700.
  • Li, Y., Huan, Li, X. Feng, Liu, J. tao, Wang, H., Fan, L. lu, Li, J., Sun, G. ping. 2018. “PKM2, a potential target for regulating cancer”. Gene, 668(October 2017), 48–53.
  • Liu, Z., Jia, X., Duan, Y., Xiao, H., Sundqvist, K. G., Permert, J., Wang, F. 2013.”Excess glucose induces hypoxia-inducible factor-1a in pancreatic cancer cells and stimulates glucose metabolism and cell migration”, Cancer Biology and Therapy, 14(5), 428–435.
  • Locasale, J. W. 2013. “Serine, glycine and one-carbon units: Cancer metabolism in full circle”, Nature Reviews. Cancer, 13(8), 572–583.
  • Locasale, J.W., Grassian, A.R., Melman, T., Lyssiotis, C.A., Mattaini, K.R., Bass, A.J., vd. 2011. “Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis”, Nature Genetics, 43(9), 869–874.
  • López-Lázaro, M. 2008. " The Warburg Effect: Why and How do Cancer Cells Activate Glycolysis in the Presence of Oxygen?", Anti-Cancer Agents in Medicinal Chemistry, 8, 305- 312.
  • Luo, W., Hu, H., Chang, R., Zhong, J., Knabel, M., O’Meally, R., vd. 2011. “Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1”, Cell, 145(5), 732–744.
  • Macheda, M. L., Rogers, S., Best, J. D. 2005. “Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer”, Journal of Cellular Physiology, 202(3), 654–662.
  • Marín-Hernandez, A., Gallardo-Perez, J.C., Hernandez-Resendiz, I., Del Mazo-Monsalvo, I., Robledo-Cadena, D.X., Moreno-Sanchez, R., Rodríguez-Enríquez, S. 2016. "Hypoglycemia Enhances Epithelial-Mesenchymal Transition and Invasiveness, and Restrains the Warburg Phenotype, in Hypoxic HeLa Cell Cultures and Microspheroids." Journal of Cellular Physiology, 232, 1346-1359.
  • Marin-Hernandez, A., Rodriguez-Enriquez, S., Vital- Gonzalez, P.A., Flores-Rodriguez, F.L., Macias-Silva, M., Sosa-Garrocho, M., Moreno-Sanchez, R. 2006. “Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an overexpressed but strongly product-inhibited hexokinase”, FEBS J, 273, 1975–1988 Medina, R.A., Owen, G.I. 2002. “Glucose transporters: expression, regulation and cancer” Biol Res, 35(1):9-26.
  • Minchenko, O., Opentanova, I., Minchenko, D., Ogura, T., Esumi, H. 2004. “Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase-4 gene via hypoxiainducible factor-1α activation”. FEBS Letters, 576(1–2), 14–20.
  • Miranda-Goncalves, V., Honavar, M., Pinheiro, C., vd. 2013. “Mono- carboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets”, Neuro-oncology. Feb 15(2):172-188.
  • Mizrak, D., Akbulut, H. 2015. “Kanser ve Açlık”, Türk Onkoloji Dergisi, 30(3), 152–157.
  • Moreno-Sánchez, R., Rodríguez-Enríquez, S., Marín-Hernández, A., Saavedra, E. 2007. “Energy metabolism in tumor cells”, FEBS Journal, 274(6), 1393–1418.
  • Moreno-Sanchez, R., Rodriguez-Enriquez, S., Saavedra, E., Marin-Hernandez, A., GallardoPerez, J. C. 2009. “The bioenergetics of cancer: Is glycolysis the main ATP supplier in all tumor cells?”, BioFactors, 35(2), 209–225.
  • Murakami, T., Nishiyama, Tç, Shirotani, T., Shinohara, Y., Kan, M., Ishii, K., Kanai, F., Nakazuru, Sç, Ebina, Y. 1992. “Identification oftwo enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes”, J Biol Chem, 267(13):9300–9306.
  • Nagamatsu, A., Umesaki, N., Li, L., Tanaka, T. 2010. Use of 18F-fluorodeoxyglucose positron emission tomography for diagnosis of uterine sarcomas, Oncol. Rep. 23, 1069–1076.
  • Nakashima, R.A., Paggi, M.G., Scott, L.J., Pedersen, P.L.1988. “Purification and characterization of bindable form of mitochondrial bound hexokinase from the highly glycolytic AS-30D rat hepatoma cell line”, Cancer Res, 48, 913–919.
  • Natsuizaka, M., Ozasa, M., Darmanin, S., Miyamoto, M., Kondo, S., Kamada, S., vd. 2007. “Synergistic up-regulation of Hexokinase-2, glucose transporters and angiogenic factors in pancreatic cancer cells by glucose deprivation and hypoxia”, Experimental Cell Research, 313(15), 3337–3348.
  • Noguchi, Y., Saito, A., Miyagi, Y., Yamanaka, S., Marat, D., Doi, C., Yoshikawa, T., Tsuburaya, A., Ito, T., Satoh, S. 2000. “Suppression of facilitative glucose transporter 1 mRNA can suppress tumor growth”, Cancer Lett, 154(2):175–18.
  • Orrock, J.M., Abbott, J.J., Gibson, L.E., Folpe, A.L. 2009. “INI1 and GLUT-1 expression in epitheloid sarcoma and its cutaneous neoplastic mimics”, Am. J. Dermatopathol., 31, 152– 156.
  • Osada-Oka, M., Hashiba, Y., Akiba, S., Imaoka, S.,Sato, T. 2010. “Glucose is necessary for stabilization of hypoxia-inducible factor-1α under hypoxia: Contribution of the pentose phosphate pathway to this stabilization”. FEBS Letters, 584(14), 3073–3079.
  • Parry, D.M., Pedersen, P.L. 1983. “Intracellular localization and properties of particulate hexokinase in the Novikoff ascites tumor”, J Biol Chem, 258, 10904–10912.
  • Pfeiffer, T., Schuster, S., Bonhoeffer, S. 2001. “Cooperation and competition in the evolution of ATP-producing pathways”, Science, 292(5516), 504–507.
  • Philipson, K.A. , Elder, M.G., White, J.O. 1985. “The effects of medroxyprogesterone acetateon enzyme activities in human endometrial carcinoma”,J. Steroid Biochem, 23, 1059- 1064.
  • Quade, B.J., Wang, T.Y., Sornberger, K., Dal Cin, P., Mutter, G.L., Morton, C.C. 2004. “Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling”, Genes Chromosom Cancer, 40, 97–108
  • Rattigan, Y.I., Patel, B.B., Ackerstaff, E., Sukenick, G., Koutcher, J. A., Glod, J.W., Banerjee, D. 2011. “Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment”, Experimental cell research, 318(4), 326–335.
  • Rodrıguez-Enrıquez, S., Jua´ ez, O., Rodrıguez-Zavala, J.S., Moreno-Sanchez, R. 2001. “Multisite control of the Crabtree effect in ascites hepatoma cells”, Eur J Biochem, 268, 2512– 2519
  • Rodríguez-Enríquez, S., Carreño-Fuentes, L., Gallardo-Pérez, J. C., Saavedra, E., Quezada, H., Vega, A., vd. 2010. “Oxidative phosphorylation is impaired by prolonged hypoxia in breast and possibly in cervix carcinoma”, International Journal of Biochemistry and Cell Biology, 42(10), 1744–1751.
  • Rodriguez-Zavala, J.S., Moreno-Sanchez, R.1998. “Modulation of oxidative phosphorylation by Mg2+ in rat heart mitochondria”, J Biol Chem 273, 7850–7855.
  • Ros, S., Schulze,A. 2013. “Balancing glycolytic flux:The role of 6-phosphofructo-2-kinase/ fructose 2,6-bisphosphatases in cancer metabolism”, Cancer Metab, 1(1),8.
  • Schwartz, L., Seyfried, T., Alfarouk K.,O., Da Veiga Moreira J., Fais, S. 2017. “Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH, Seminars in Cancer Biology”, Seminars in Cancer Biology, 43, 134-138.
  • Sciacovelli, M., Gaude, E., Hilvo, M., Frezza, C. 2014. “The metabolic alterations of cancer cells”, Methods Enzymol.,542:1-23.
  • Seagroves, T.N., Ryan, H.E., Lu, H., Wouters, B.G,. Knapp, M. Thibault, P. Laderoute, K. Johnson, R.S. 2001. Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells, Mol. Cell. Biol. 21 3436–3444.
  • Seshagiri, P.B., Bavister, B.D.1991. Glucose and phos- phate inhibit respiration and oxidative metabolism in cultured hamster eight-cell embryos: evidence for the ‘crabtree effect’. Mol Reprod Dev 30, 105–111.
  • Shackelford, D.B., Shaw, R.J. 2009. “The LKB1-AMPK pathway: metabolism and growth control in tumor suppression”, Nat Rev Cancer. August ;,9(8), 563–575.
  • Shim, H., Dolde, C., Lewis, B. C., Wu, C. S., Dang, G., Jungmann, R. A, Dalla-Favera R., Dang C.V. 1997. “c-Myc transactivation of LDH-a: Implications for tumor metabolism and growth”, Proceedings of the National Academy of Sciences of the United States of America, 94(13), 6658–6663.
  • Smolková, K., Bellance, N., Scandurra, F., Génot, E., Gnaiger, E., Plecitá-Hlavatá, L., Jezek, P., Rossignol, R. 2010. “Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia”, J Bioenerg Biomembr, Feb;42(1):55-67.
  • Soga, T. 2013. “Cancer metabolism: Key players in metabolic reprogramming”, Cancer Science, 104(3), 275–281.
  • Soule, H., Vazquez, J., Long, A., Albert, S., Brennan, M. 1973. “Human cell line from a pleural effusion derived from a breast carcinoma”. M. J Natl Cancer Inst, 51, 1409–1416.
  • Stanton, R.C. 2012. “Glucose-6-phosphate dehydrogenase, NADPH, and cell survival”, IUBMB Life, 64,362–369.
  • Su, L.J., Chang, C.W., Wu, Y.C., Chen, K.C., Lin, C.J., Liang, S.C., Lin, C.H., Whang Peng, J., Hsu, S.L., Chen, C.H., Huang, C.Y. 2007. “Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data using a block bootstrap re-sampling scheme”, BMC Genomics, 8,140.
  • Sugiura, K., Benedict, S. R. 1929. “The action of certain dye stuffs on the growth of transplantable tumors”, The Journal of Cancer Research, 13(4), 340–358.
  • Szablewski, L. 2013. “Expression of glucose transporters in cancers”, Biochimica et Biophysica Acta - Reviews on Cancer, 1835(2), 164–169.
  • Tomlinson, I. P. M., Alam, N. A., Rowan, A. J., Barclay, E., Jaeger, E. E. M., Kelsell, D., vd. 2002. “Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer”, Nature Genetics, 30(4), 406–410.
  • Vadlakonda, L., Dash, A., Pasupuleti, M., Anil Kumar, K., Reddanna, P. (2013. “Did we get pasteur, warburg, and crabtree on a right note?”, Frontiers in oncology, 3, 186.
  • Vander Heiden, M.G, Cantley L.C., Thompson, C.B. 2009. “Understanding the Warburg effect: the metabolic requirements of cell proliferation”, Science, 324:1029–1033.
  • Vander Heiden, M.G., Christofk, H.R., Schuman, E., Subtelny, A.O., Sharfi, H., Harlow, E.E., Xian, J., Cantley, L.C. 2010.” Identification ofsmall molecule inhibitors ofpyruvate kinase M2”, Biochemical Pharmacology, 79(8), 1118–1124.
  • Van Driel, B.E., Valet, G.K., Lyon, H., Hansen, U., Song, J.Y., Van Noorden, C.J. 1999. "Prognostic estimation of survival of colorectal cancer patients with the quantitative histochemical assay of G6PDH activity and the multi-parameter classification program CLASSIF1", Cytometry 38 (4), 176–183.
  • Vizan, P., Alcarraz-Vizan, G., Diaz-Moralli, S., Solovjeva, O. N., Frederiks, W. M., Cascante, M. 2009. “Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29”, International Journal of Cancer, 124(12), 2789–2796.
  • Vordermark, D., Kraft, P., Katzer, A., Bölling, T., Willner, J., & Flentje, M. 2005. “Glucose requirement for hypoxic accumulation of hypoxia-inducible factor-1α (HIF-1α)”, Cancer Letters, 230(1), 122–133.
  • Wahdan-Alaswad, R., Fan, Z., Edgerton, S.M., Liu, B., Deng, X., Arnadottir, S., Richer, J., Anderson, S., Thor, A. 2013. "Glucose promotes breast cancer aggression and reduces metformin efficacy" Cell Cycle, 12:24, 3759–3769
  • Wang, J., Yuan, W., Chen, Z., Wu, S., Chen, J., Ge, J. Hou, F., Chen, Z. 2012. “Overexpression of G6PD is associated with poor clinical outcome in gastric cancer”, Tumour Biol, 33, 95–101.
  • Ward, P. S., & Thompson, C. B. 2012. “Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate”, Cancer Cell, 21(3), 297–308.
  • Weinhouse, S. 1976. “Warburg hypothesis 50 years later”, Zeitschrift Fur Krebsforschung Und Klinische Onkologie, 87(2), 115–126.
  • Wigerup, C., Påhlman, S., Bexell, D. 2016. " Therapeutic targeting of hypoxia and hypoxiainducible factors in cancer." Pharmacology & Therapeutics, 164, 152–169. Wilson, J.E. 2003. “Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function”, J Exp Biol.; 206:2049–2057.
  • Wingo, S.N., Gallardo, T.D., Akbay, E.A., Liang, M-C., Contreras, C.M., Boren, T., vd. 2009. “Somatic LKB1 Mutations Promote Cervical Cancer Progression”, PLoS ONE 4(4), e5137.
  • Wong T. L., Che, N., Ma, S. 2017. "Reprogramming of central carbon metabolism in cancer stem cells", Biochimica et Biophysica Acta - Molecular Basis of Disease, 1863 (7), 1728-1738.
  • Wood, I.S., Trayhurn,P. 2003. ”Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins”,Br J Nutr. 2003 Jan;89(1):3-9.
  • Yalcin, A., Telang, S., Clem, B., Chesney, J. 2009. “Regulation ofglucose metabolism by 6- phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer”. Experimental and Molecular Pathology, 86(3), 174–179.
  • Yang, X., Borg, L.A., Eriksson, U.J. 1997. Altered metabolism and superoxide generation in neural tissue of rat embryos exposed to high glucose. Am J Physiol 272,173-80.
  • Yang, Y.C., Cheng, T.Y., Huang, S.M., Su, C.Y., Yang, P.W., Lee, J.M., Chen, C.K., Hsiao, M., Hua, K.T., Kuo, M.L. 2015. “Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association”. Oncogene 35 (26), 3387.
  • Yi, W., Clark, P.M., Mason, D.E., Keenan, M.C., Hill, C., Goddard, W. A., Peters. E.C., Driggers, E.M., Hsieh-Wilson, L.C. 2012. “Phosphofructokinase 1 glycosylation regulates cell growth and metabolism”. Science, 337(6097), 975–980.
  • Yin, L.M., Wei, Y., Wang, Y., Xu, Y.D., Yang, Y.Q. 2013. " Long Term and Standard Incubations of WST-1 Reagent Reflect the Same Inhibitory Trend of Cell Viability in Rat Airway Smooth Muscle Cells" International Journal of Medical Sciences, 10 (1), 68-72.
  • Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K.I., Dang, C.V., Semenza, G.L. 2007. " HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHLdeficient renal cell carcinoma by repression of C-MYC activity." Cancer Cell, 11(5), 407–420.
  • Zhang, J., Nuebel, E., Daley, G. Q., Koehler, C. M., Teitell, M. A. 2012. “Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal”. Cell Stem Cell, 11(5), 589– 595.
  • Zhang, J., Zhang, F., Hong, C., Giuliano, A. E., Cui, X., Zhou, G. 2015. “Critical protein GAPDH and its regulatory mechanisms in cancer cells”, Cancer Biol Med, 12(1), 10–22.
  • Zu, X. L., Guppy, M. 2004. “Cancer metabolism: Facts, fantasy, and fiction”, Biochemical and Biophysical Research Communications, 313(3), 459–465.
  • Zhu, S., Yao, F., Li, W.H., Wan, J.N., Zhang, Y.M., Tang, Z., Khan, S., Wang, C.H., Sun, S.R. 2013. " PKCδ-dependent Activation of the Ubiquitin Proteasome System is Responsible for High Glucose-induced Human Breast Cancer MCF-7 Cell Proliferation, Migration and Invasion", Asian Pacific Journal of Cancer Prevention, 14 (10), 5687-5692.
APA BİLDİK A, KIRAL F, EKREN ASICI G (2019). MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. , 1 - 102.
Chicago BİLDİK Ayşehül,KIRAL Funda Kargın,EKREN ASICI GAMZE SEVRI MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. (2019): 1 - 102.
MLA BİLDİK Ayşehül,KIRAL Funda Kargın,EKREN ASICI GAMZE SEVRI MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. , 2019, ss.1 - 102.
AMA BİLDİK A,KIRAL F,EKREN ASICI G MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. . 2019; 1 - 102.
Vancouver BİLDİK A,KIRAL F,EKREN ASICI G MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. . 2019; 1 - 102.
IEEE BİLDİK A,KIRAL F,EKREN ASICI G "MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması." , ss.1 - 102, 2019.
ISNAD BİLDİK, Ayşehül vd. "MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması". (2019), 1-102.
APA BİLDİK A, KIRAL F, EKREN ASICI G (2019). MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. , 1 - 102.
Chicago BİLDİK Ayşehül,KIRAL Funda Kargın,EKREN ASICI GAMZE SEVRI MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. (2019): 1 - 102.
MLA BİLDİK Ayşehül,KIRAL Funda Kargın,EKREN ASICI GAMZE SEVRI MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. , 2019, ss.1 - 102.
AMA BİLDİK A,KIRAL F,EKREN ASICI G MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. . 2019; 1 - 102.
Vancouver BİLDİK A,KIRAL F,EKREN ASICI G MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması. . 2019; 1 - 102.
IEEE BİLDİK A,KIRAL F,EKREN ASICI G "MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması." , ss.1 - 102, 2019.
ISNAD BİLDİK, Ayşehül vd. "MCF-7 Meme Kanser Hücre Hattında Warburg Etkisinin ve Hipoksinin Glikoliz Enzimleri Gen Ekspresyonu Düzeyinde Araştırılması". (2019), 1-102.