Progesterone Induces Erk1/2 through an EGFR and G Proteins-Dependent Pathway in MCF-7 Breast Cancer Cells
Fernando Candanedo-Gonzalez, Adriana Soto-Guzman, Pedro Cortes-Reynosa, Eduardo Perez-Salazar. Cinvestav-IPN, Mexico City, Mexico
Background: In Mexico, breast cancer is the second most frequent malignancy, occurs in 46% of women younger than 50 years of age. About 75% of breast tumors are positive for the progesterone receptor. Evidence that progesterone is a steroid hormone that regulates breast cancer functions is accumulating. However, the signal transduction pathways activated by progesterone have not been studied in detail. To investigate the influence of progesterone on MCF-7 breast cancer cells and determine that signal transduction pathways modulates.
Design: MCF-7 breast cancer cells were cultured in DMEM and were serum-starved for 12 h before treatment with inhibitors (GFI, PTX, CTX, AG1478, GM6001, PP2 and PP3) and/or progesterone (100 nM) for 30 min and evaluated by electrophoretic mobility shift assay, and Western blot. Statistical analysis: Results are expressed as mean ± SD. Data was statistically analyzed using one-way ANOVA. Statistical probability of p < 0.05 was considered significant.
Results: Our results demonstrate that stimulation of MCF-7 cells with progesterone promoted the rapidly phosphorylation of ERK1/2 at Thr-202 and Tyr-204, in a time and concentration-dependent manner. The inhibition with AG1478 completely prevented ERK1/2 activation. Also showed that inhibition of MMPs activity did not prevent ERK1/2 activation. In contrast, treatment of cells with PP2 completely inhibited ERK1/2 activation induced by progesterone, while treatment with PP3 did not inhibit ER1/2 activation. Treatment of cells with GFI, PTX and CTX inhibited ERK1/2 activation induced by progesterone. On the other hand, progesterone induces NFkB activation through G proteins-dependent pathway.
Conclusions: these results showed that progesterone induces ERK1/2 activation through EGFR and G protein-dependent pathway in MCF-7 breast cancer cells. Also, suggest that the progesterone effects in cancer breast cells can be mediated through induction of the NFkB-DNA complex formation and consequently through modulation of the NFkB dependent gene expression. Understanding the role of the hormone progesterone and its receptor in breast cancer, will allow to offer new therapeutic options in the future.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 282, Wednesday Morning