BioProject

The initiation of breast cancer is associated with increased expression of tumor-promoting estrogen receptor α (ERα) protein and decreased expression of tumor-suppressive ERβ protein. More...

The initiation of breast cancer is associated with increased expression of tumor-promoting estrogen receptor α (ERα) protein and decreased expression of tumor-suppressive ERβ protein. However, the mechanism underlying this process is unknown. Here we show that Pescadillo/PES1, an estrogen-inducible protein that is over-expressed in breast cancer, can regulate the balance between ERα and ERβ. PES1 enhances transcriptional activity of ERα and reduces that of ERβ, and modulates many estrogen-responsive genes. Consistent with this regulation of ERα and ERβ transcriptional activity, PES1 increases the stability of the ERα protein and decreases that of ERβ through the ubiquitin-proteasome pathway, mediated by the carboxyl terminus of Hsc70-interacting protein (CHIP). Moreover, PES1 can transform normal human mammary epithelial cells and is required for estrogen-induced breast tumor growth in nude mice. Further analysis of clinical samples showed that expression of PES1 correlates positively with ERα expression and negatively with ERβ expression, and predicts good clinical outcome in breast cancer. Our data demonstrate that PES1 contributes to breast tumor growth through regulating the balance between ERα and ERβ and may be a better target for the development of drugs that selectively regulate ERα and ERβ activities. Overall design: Three samples: Control siRNA -E2 vs. Control siRNA +E2, Control siRNA -E2 vs. PES1 siRNA -E2,Control siRNA -E2 vs. PES1 siRNA +E2 Less...