Chronic Leptin Treatment Sensitizes MCF-7 Breast Cancer Cells to Estrogen

Cellular Physiology and Biochemistry

关键词: Estrogen receptor;    MCF-7;    Leptin;    Estrogen;    Breast cancer;    Obesity;   

DOI  :  10.1159/000335796

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Obesity is associated with an increased risk of estrogen-dependent breast cancer. The adipokine leptin, whose levels are chronically increased in obese people, has been shown to stimulate ER positive cancer cell growth. Considering previous evidence of a crosstalk between leptin and estrogen signaling, the objective of this study was to establish the influence of chronic leptin treatment on estrogen-dependent cell growth. Methods To this aim, we use the estrogen receptor (ER) positive MCF-7 breast cancer cell line treated chronically with leptin and analyzed estrogen-dependent cell growth, ERs (ERα and ERβ) expression, ER-dependent transcriptional activity as well as cell survival to the antiestrogenic agents tamoxifen and ICI 182,780. Results Leptin signaling pathway kept activated after chronic stimulation (7 days) with leptin showing significant phosphorylation of JAK2 and STAT3 and higher cell proliferation rate. Chronic leptin at 100 ng/mL dose increased ERα to ERβ ratio and consistently enhanced estrogen-dependent transcriptional activity, increasing E2-dependent cell growth and resistance to antiestrogen agents. Conclusion This study supports the existence of a crosstalk between leptin and estrogen, in which leptin might play an important role potentiating the mitogenic action of estrogen, probably by alteration of ERα to ERβ ratio.

【 授权许可】

CC BY-NC-ND