Novel role for PINX1 as a coregulator of nuclear hormone receptors

Abstract Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process influenced by coactivator and corepressor proteins. This work shows that Pin2 interacting protein 1 (PINX1) interacts with the N-terminal domain of ERα and functions as a corepressor of ERα. Furthermore, it represses both AF-1 and AF-2 transcriptional activities. Chromatin immunoprecipitation assays verified that the interaction between ERα and PINX1 occurs on E 2 regulated promoters and enhanced expression of PINX1 deregulates the expression of a number of genes that have a role in cell growth and proliferation in breast cancer. PINX1 overexpression decreases estrogen mediated proliferation of breast cancer cell lines, while its depletion shows the opposite effect. Taken together, these data show a novel molecular mechanism for PINX1 as an attenuator of estrogen receptor activity in breast cancer cell lines, furthering its role as a tumor suppressor gene in breast cancer.