Progesterone Induces NF-kB Activation through PI3K/Akt-2 Signal Pathway Which Regulates Focal Adhesion Kinase (FAK) in MCF-7 Breast Cancer
Fernando Candanedo-Gonzalez, Roberto Espinosa-Neira, Socrates Villegas-Comonfort, Nathalia Serna Marquez, Pedro Cortes-Reynosa, Eduardo Perez Salazar. Oncology Hospital, National Medical Center Century XXI, IMSS, Mexico City, Mexico; CINVESTAV-IPN, Mexico City, Mexico
Background: Around 75% of breast tumors are positive for the progesterone receptor (PR). However, the signal transduction pathways activated by progesterone have not been studied in detail. The phosphatidyl inositol 3-kinase (PI3K) pathway plays an important role in breast cancer progression. Downstream of PI3K, Akt1 and Akt2, have opposing roles in breast cancer invasion migration, which lead to metastatic dissemination in endocrine-treated breast cancer. Objective: To study the signal transduction pathways mediated by progesterone on MCF-7 breast cancer cells.
Design: MCF-7 breast cancer cells were cultured in DMEM, serum-starved for 12 h, and treated with inhibitors (Wortmannin, rapamicin, PP2) and/or progesterone (100 nM). FAK and Akt2 activation were analyzed by Western blotting using antibodies against phosphorylated specific amino acid residues. NFκB activation was analyzed by EMSA. Statistical analysis: Results are expressed as mean ± SD. Data were statistically analyzed using one-way ANOVA. Statistical probability of p < 0.05 was considered significant.
Results: Stimulation of MCF-7 cells with 100 nM progesterone promoted Akt2 activation through a PI3K dependent pathway, as well as FAK activation in a time-dependent manner. Moreover, progesterone induces NFκB activation in a time-dependent manner and it was dependent on PI3K, mTOR, Src and microtubule integrity.
Conclusions: Progesterone induces Akt2, FAK and NFκB activation through PI3K-dependent pathway in MCF-7 breast cancer cell. Our findings delineate a new signal transduction pathway mediated by progesterone in breast cancer cells. The understanding of these pathways will allow to offer new therapeutic options in the future.
Monday, March 4, 2013 1:00 PM
Poster Session II # 270, Monday Afternoon