Effects of different glucose concentrations on the leptin signaling pathway in MCF-7 and T47D breast cancer cells

Abstract

Aim: Leptin activates multiple intracellular signaling pathways, including JAK/STAT, by binding to its receptor. Leptin is also an important 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 is not known. The aim of this study was to investigate the effect of different glucose concentrations on the leptin signaling pathway in MCF-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 in different 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 and T47D cells compared to 0 mM glucose incubated cells (P<0.001). mRNA levels of leptin, ObR, ObRb or STAT3 in 2.5 mM, 5 mM, 25 mM, or 50 mM glucose incubated cells were not significantly different in both cell lines compared to 0 mM (p>0.05). 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<0.05). Conclusion: Our data suggest that the enhancing effect of glucose on breast cancer cell proliferation is not mediated by the JAK/STAT pathway.

Glucose deprivation reduces proliferation and motility, and enhances the anti-proliferative effects of paclitaxel and doxorubicin in breast cell lines in vitro

“…Hyperglycemia has been shown to contribute to enhanced breast cancer cell proliferation, metastasis and chemotherapy resistance [8,[32][33][34]. Furthermore, glucose and other factors involved in glucose metabolism such as insulin and insulin like growth factors enhance breast cancer cell proliferation and contribute to breast cancer development [35][36][37][38]. High glucose concentration (25-50 mM) significantly enhanced MCF-7 and T47D cell proliferation and decreased cell apoptosis and necrosis, while low glucose concentration (2.5 mM) induced cell apoptosis and necrosis [37].…”

“…Furthermore, glucose and other factors involved in glucose metabolism such as insulin and insulin like growth factors enhance breast cancer cell proliferation and contribute to breast cancer development [35][36][37][38]. High glucose concentration (25-50 mM) significantly enhanced MCF-7 and T47D cell proliferation and decreased cell apoptosis and necrosis, while low glucose concentration (2.5 mM) induced cell apoptosis and necrosis [37]. In addition, high glucose concentration (25 mM) in the culture medium of MCF-7 and T47D enhanced IGF-1 induced cell growth; this was not observed when cells were cultured in low glucose containing medium (5 mM) [39].…”

Prioritizing and characterizing functionally relevant genes across human tissues

“…In Ovary, resting TPE interval was enriched for by both gene lists. TPE intervals have been implicated in premature ovarian failure [27]. A seemingly disconnected association uniquely captured by the FUGUE is squamous cell lung carcinoma (SCLC).…”