HMGCR GENE EXPRESSION IN DIFFERENT BREAST CANCER CELL LINES

Year 2022, Volume: 5 Issue: 2, 12 - 19, 30.08.2022

Başak Şentürk , Ahsen Merve Bayrak , Burcu Yücel

Abstract

Keywords

Breast cancer, HMGCR, Cholesterol metabolism

Supporting Institution

Technological Research Council of Turkey (TÜBİTAK) 3501-Career Development Program

Project Number

118S351

Thanks

We would like to thank the Science and Advanced Technology Application and Research Center (BİLTAM) for facilities and the Scientific and Technological Research Council of Turkey (TÜBİTAK) 3501-Career Development Program for financial support.

HMGCR GENE EXPRESSION IN DIFFERENT BREAST CANCER CELL LINES

Abstract

Breast cancer is the one of the most common cancer types among women in the world. Breast cells can be divided uncontrollably in either lobules or ducts. Breast cancer can be in situ or invasive, depending on its type. Cholesterol homeostasis is an important parameter for cancer progression. In normal cells, cholesterol is tightly regulated with de nova synthesis named as mevalonate pathway. In this pathway, important intermediates are produced for production of cholesterol. In the first step of the pathway, 3-hydroxy-3-methylglutaryl coenzyme A, known as HMG-CoA, is converted to mevalonate by the rate-limiting enzyme HMGCR and the final product is farnesyl pyrophosphate called FPP, which is the building block of cholesterol. In this study, we aimed to determine the expression levels of the HMGCR gene, which encodes 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme, in different breast cancer cell lines: MDA-MB 231, MDA-MB 435, MDA-MB 453, UACC 2080, MCF-7, HCC 1938 via real-time PCR. As a result, we found that the MCF7 cell line has the lowest level of HMGCR mRNA, and the MDA-MB-453 cell line has the highest level of HMGCR mRNA. Differences in expression levels may be due to hormone receptors. Furthermore, other triple negative cell lines showed different expression levels among themselves, although they expressed more HMGCR than MCF-7. The reason for this was thought to be related to the location of cancer formation or the age of the patient.

Keywords

Breast cancer, HMGCR, Cholesterol metabolism

Project Number

118S351

References

• Bjarnadottir, O., Feldt, M., Inasu, M., Bendahl, P., Elebro, K., Kimbung, S., & Borgquist, S. (2020). Statin use, HMGCR expression, and breast cancer survival – The Malmö Diet and Cancer Study. Scientific Reports, 10(1). doi: 10.1038/s41598-019-57323-9 Breast cancer. (2021). Retrieved 24 July 2022, from https://www.who.int/news-room/fact-sheets/detail/breast-cancer
• Burstein, H., Polyak, K., Wong, J., Lester, S., & Kaelin, C. (2004). Ductal Carcinoma in Situ of the Breast. New England Journal Of Medicine, 350(14), 1430-1441. doi: 10.1056/nejmra031301
• Chimento A, Casaburi I, Avena P, Trotta F, De Luca A, Rago V, Pezzi V, Sirianni R. Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment. Front Endocrinol (Lausanne). 2019 Jan 21;9:807. doi: 10.3389/fendo.2018.00807. PMID: 30719023; PMCID: PMC6348274.
• Clendening, J., & Penn, L. (2012). Targeting tumor cell metabolism with statins. Oncogene, 31(48), 4967-4978. doi: 10.1038/onc.2012.6
• Clendening JW, Pandyra A, Boutros PC, El Ghamrasni S, Khosravi F, Trentin GA, Martirosyan A, Hakem A, Hakem R, Jurisica I, Penn LZ. Dysregulation of the mevalonate pathway promotes transformation. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15051-6. doi: 10.1073/pnas.0910258107. Epub 2010 Aug 9. PMID: 20696928; PMCID: PMC2930553.
• Creighton, C. (2012). The molecular profile of luminal B breast cancer. Biologics: Targets And Therapy, 289. doi: 10.2147/btt.s29923
• Danilo, C., & Frank, P. (2012). Cholesterol and breast cancer development. Current Opinion In Pharmacology, 12(6), 677-682. doi: 10.1016/j.coph.2012.07.009
• Demircan, B., Yucel, B., & Radosevich, J. (2019). DNA Methylation in Human Breast Cancer Cell Lines Adapted to High Nitric Oxide. In Vivo, 34(1), 169-176. doi: 10.21873/invivo.11758
• Desai, S., Moonim, M., Gill, A., Punia, R., Naresh, K., & Chinoy, R. (2000). Hormone receptor status of breast cancer in India: a study of 798 tumours. The Breast, 9(5), 267-270. doi: 10.1054/brst.2000.0134
• Ding, X., Zhang, W., Li, S., & Yang, H. (2019). The role of cholesterol metabolism in cancer. American journal of cancer research, 9(2), 219–227.
• Frykberg ER, Bland KI. In situ breast carcinoma. Advances in Surgery. 1993 ;26:29-72. PMID: 8380307.
• Goldstein, J., & Brown, M. (1990). Regulation of the mevalonate pathway. Nature, 343(6257), 425-430. doi: 10.1038/343425a0
• Göbel, A., Breining, D., Rauner, M., Hofbauer, L., & Rachner, T. (2019). Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells. Cell Death & Disease, 10(2). doi: 10.1038/s41419-019-1322-x
• Göbel, A., Rauner, M., Hofbauer, L., & Rachner, T. (2020). Cholesterol and beyond - The role of the mevalonate pathway in cancer biology. Biochimica Et Biophysica Acta (BBA) - Reviews On Cancer, 1873(2), 188351. doi: 10.1016/j.bbcan.2020.188351
• Gruvberger S, Ringnér M, Chen Y, Panavally S, Saal LH, Borg A, Fernö M, Peterson C, Meltzer PS. Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns. Cancer Res. 2001 Aug 15;61(16):5979-84. PMID: 11507038.
• Gustbée, E., Tryggvadottir, H., Markkula, A., Simonsson, M., Nodin, B., & Jirström, K. et al. (2015). Tumor-specific expression of HMG-CoA reductase in a population-based cohort of breast cancer patients. BMC Clinical Pathology, 15(1). doi: 10.1186/s12907-015-0008-2
• Karlic, H., & Varga, F. (2017). Mevalonate Pathway. Reference Module In Biomedical Sciences. doi: 10.1016/b978-0-12-801238-3.65000-6
• Li, Y., Park, M., Ye, S., Kim, C., & Kim, Y. (2006). Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents. The American Journal Of Pathology, 168(4), 1107-1118. doi: 10.2353/ajpath.2006.050959
• McGuire, W., Horwitz, K., Pearson, O., & Segaloff, A. (1977). Current status of estrogen and progesterone receptors in breast cancer. Cancer, 39(6), 2934-2947. doi: 10.1002/1097-0142(197706)39:6<2934::aid-cncr2820390680>3.0.co;2-p
• Mok, E., & Lee, T. (2020). The Pivotal Role of the Dysregulation of Cholesterol Homeostasis in Cancer: Implications for Therapeutic Targets. Cancers, 12(6), 1410. doi: 10.3390/cancers12061410
• Murai, T. (2012). The Role of Lipid Rafts in Cancer Cell Adhesion and Migration. International Journal Of Cell Biology, 2012, 1-6. doi: 10.1155/2012/763283
• Posner, M., & Wolmark, N. (1992). Non-invasive breast carcinoma. Breast Cancer Research And Treatment, 21(3), 155-164. doi: 10.1007/bf01974998
• Ross, J., Slodkowska, E., Symmans, W., Pusztai, L., Ravdin, P., & Hortobagyi, G. (2009). The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine. The Oncologist, 14(4), 320-368. doi: 10.1634/theoncologist.2008-0230
• Silvente-Poirot, S., & Poirot, M. (2012). Cholesterol metabolism and cancer: the good, the bad and the ugly. Current Opinion In Pharmacology, 12(6), 673-676. doi: 10.1016/j.coph.2012.10.004
• Sun, L., Ding, H., Jia, Y. et al. Associations of genetically proxied inhibition of HMG-CoA reductase, NPC1L1, and PCSK9 with breast cancer and prostate cancer. Breast Cancer Res 24, 12 (2022). https://doi.org/10.1186/s13058-022-01508-0
• Turashvili G, Bouchal J, Burkadze G, Kolár Z. Differentiation of tumours of ductal and lobular origin: I. Proteomics of invasive ductal and lobular breast carcinomas. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2005 Jun;149(1):57-62. DOI: 10.5507/bp.2005.005. PMID: 16170389.