RBCK1 drives breast cancer cell proliferation by promoting transcription of estrogen receptor α and cyclin B1

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 G₂-M phase of the cell cycle, decreased proliferation, and reduced mRNA levels for ERα and its target genes cyclin D1 and c-myc. 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. G₂-M phase arrest was mediated independently from reduced ERα levels, instead associated with transcriptional inhibition of the key G₂-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.