Effects of different glucose concentrations on the leptin signaling pathway in MCF-7 and T47D breast cancer cells
Effects of different glucose concentrations on the leptin signaling pathway in MCF-7 and T47D breast cancer cells
Aim: Leptin activates multiple intracellular signaling pathways, including JAK/STAT, by binding to its receptor. Leptin is also animportant regulator of glucose homeostasis. Although both glucose and leptin increase breast cancer cell proliferation in vitro,whether the enhancing effect of glucose on the proliferation of breast cancer cells is mediated by the leptin signaling pathway isnot known. The aim of this study was to investigate the effect of different glucose concentrations on the leptin signaling pathway inMCF-7 and T47D breast cancer cells.Material and Methods: MCF-7 and T47D cell proliferation in different glucose concentrations (2.5 mM, 5 mM, 25 mM, or 50 mM)were assayed using CCK-8 assay. Leptin, leptin receptors (ObR, ObRb) as well as STAT3 mRNA and protein levels in both cell lines indifferent glucose concentrations were examined by RT-PCR and western blot, respectively.Results: Incubation in 2.5 mM, 5 mM, 25 mM, or 50 mM glucose for 72h significantly increased the proliferation of both MCF-7 andT47D cells compared to 0 mM glucose incubated cells (P0.05). However,ObR protein levels in MCF-7 cells incubated in 25 mM glucose was significantly lower compared to 0 mM glucose by western blot(p
___
- 1. Bronsveld HK, Jensen V, Vahl P, et al. Diabetes and Breast Cancer Subtypes. PLoS One 2017;12:0170084.
- 2. Liao S, Li J, Wei W, et al. Association between diabetes mellitus and breast cancer risk: a meta-analysis of the literature. Asian Pac J Cancer Prev 2011;12:1061-5.
- 3. Boyle P, Boniol M, Koechlin A, et al. Diabetes and breast cancer risk: a meta-analysis. Br J Cancer 2012;107:1608-17.
- 4. Lipscombe LL, Goodwin PJ, Zinman B, et al. The impact of diabetes on survival following breast cancer. Breast Cancer Res Treat 2008;109:389-95.
- 5. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569-78.
- 6. Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 2010;123:627-35.
- 7. Chan DS, Vieira AR, Aune D, et al. Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies Ann Oncol 2014;25:1901-14.
- 8. Boden G, Chen X, Mozzoli M, et al. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 1996;81:3419-23.
- 9. Dubuc GR, Phinney SD, Stern JS, et al.Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 1998;47:429-34.
- 10. Mizuno T, Bergen H, Kleopoulos S, et al. Effects of nutritional status and aging on leptin gene expression in mice: importance of glucose. Horm Metab Res 1996;28:679-84.
- 11. Yang M, Peng S, Li W, et al. Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population. Sci Rep 2016;6:23948.
- 12. Dutta D, Ghosh S, Pandit K, et al. Leptin and cancer: Pathogenesis and modulation. Indian J Endocrinol Metab 2012;16:596-600.
- 13. Pan WW, Myers MG Jr. Leptin and the maintenance of elevated body weight. Nat Rev Neurosci 2018;19:95- 105.
- 14. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normalweight and obese humans. N Engl J Med 1996; 334:292-5.
- 15. Maffei M, Halaas J, Ravussin E, at el. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995;1:1155-61.
- 16. Wu MH, Chou YC, Chou WY, et al. Circulating levels of leptin, adiposity and breast cancer risk. Br J Cancer 2009;100:578-82.
- 17. Hu X, Juneja SC, Maihle NJ, et al. Leptin--a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst 2002;94:1704-11.
- 18. Tahergorabi Z, Khazaei M. Leptin and its cardiovascular effects: Focus on angiogenesis. Adv Biomed Res 2015;4:79.
- 19. Rose DP, Gilhooly EM, Nixon DW. Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review). Int J Oncol 2002;21:1285- 92.
- 20. Cirillo D, Rachiglio AM, la Montagna R, et al. Leptin signaling in breast cancer: an overview. J Cell Biochem 2008;105:956-64
- 21. Artac M, Altundag K. Leptin and breast cancer: an overview. Med Oncol 2012;29:1510-4.
- 22. Ishikawa M, Kitayama J, Nagawa H. Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res 2004;10:4325- 31.
- 23. Hou Y, Zhou M, Xie J, et al. High glucose levels promote the proliferation of breast cancer cells through GTPases. Breast Cancer (Dove Med Press) 2017;9:429-36.
- 24. Liang X, Wang S, Wang X, et al. Leptin promotes the growth of breast cancer by upregulating the Wnt/βcatenin pathway. Exp Ther Med 2018;16:767-71.
- 25. Lim LY, Vidnovic N, Ellisen LW, et al. Mutant p53 mediates survival of breast cancer cells. Br J Cancer 2009;101:1606-12.
- 26. Sheikhpour R. Leptin in Breast Cancer: Its Relationship with Insulin, Estrogens and Oxidative Stress. IJBC 2017;9:1-4.
- 27. Dubois V, Jardé T, Delort L, et al. Leptin induces a proliferative response in breast cancer cells but not in normal breast cells. Nutr Cancer 2014;66:645-55.
- 28. Wei ML, Duan P, Wang ZM, et al. High glucose and high insulin conditions promote MCF-7 cell proliferation and invasion by upregulating IRS1 and activating the Ras/Raf/ERK pathway. Mol Med Rep 2017;16:6690-6.
- 29. Sun S, Sun Y, Rong X, et al. High glucose promotes breast cancer proliferation and metastasis by impairing angiotensinogen expression. Biosci Rep 2019;39:BSR20190436.
- 30. Frankenberry KA, Skinner H, Somasundar P, et al. Leptin receptor expression and cell signaling in breast cancer. Int J Oncol 2006;28:985-93.
- 31. Mullen M, Gonzalez-Perez RR. Leptin-Induced JAK/ STAT Signaling and Cancer Growth. Vaccines (Basel) 2016;4:26.
- 32. Vona-Davis L, Skinner H, Jackson B, et al. Leptin activates MAPK signaling in human breast and prostate cancer. J Surg Res 2003;114:300-1.