Novel role for PINX1 as a coregulator of nuclear hormone receptors

作者：Noriega Reyes Maria Yamilet; Rivas Torres Miguel Angel; Onate Ocana Luis Fernando; Valles Albert Jordan; Baranda Avila Noemi; Langley Elizabeth^*

来源：Molecular and Cellular Endocrinology, 2015, 414(C): 9-18.

DOI：10.1016/j.mce.2015.07.011

• Estrogen receptor
• Breast cancer
• PINX1
• Corepressors and transcriptional regulation

Estrogen receptor alpha (ER alpha) has an established role in breast cancer biology. Transcriptional activation by ER alpha 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 Elta and functions as a corepressor of ER alpha Furthermore, it represses both AF-1 and AF-2 transcriptional activities. Chromatin immunoprecipitation assays verified that the interaction between ER alpha 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.

• 出版日期2015-10-15