Data from RBCK1 Drives Breast Cancer Cell Proliferation by Promoting Transcription of Estrogen Receptor α and Cyclin B1

Abstract

<div>Abstract<p>Cell cycle regulatory pathways in breast cancer are incompletely described. Here, we report an important role in estrogen receptor α (ERα)–positive breast cancer cells for the protein kinase C1 (PKC1)–interacting protein RBCK1 in supporting cell cycle progression by driving transcription of ERα and cyclin B1. RBCK1-depleted cells exhibited increased accumulation in G<sub>2</sub>-M phase of the cell cycle, decreased proliferation, and reduced mRNA levels for ERα and its target genes cyclin D1 and c-<i>myc</i>. Chromatin immunoprecipitation revealed that ERα transcription is associated with RBCK1 recruitment to the ERα promoter, suggesting that transcriptional regulation is one mechanism by which RBCK1 affects ERα mRNA levels. G<sub>2</sub>-M phase arrest was mediated independently from reduced ERα levels, instead associated with transcriptional inhibition of the key G<sub>2</sub>-M regulator cyclin B1. In breast tumor samples, there was a positive correlation between levels of RBCK1, ERα, and cyclin B1 mRNA levels. Our findings suggest that RBCK1 regulates cell cycle progression and proliferation of ERα-positive breast cancer cells by supporting transcription of ERα and cyclin B1. Cancer Res; 70(3); 1265–74</p></div>