TY - JOUR
T1 - RBCK1 drives breast cancer cell proliferation by promoting transcription of estrogen receptor α and cyclin B1
AU - Gustafsson, Nina
AU - Zhao, Chunyan
AU - Gustafsson, Jan Åke
AU - Dahlman-Wright, Karin
PY - 2010/2/1
Y1 - 2010/2/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-09-2674
DO - 10.1158/0008-5472.CAN-09-2674
M3 - Article
C2 - 20103625
AN - SCOPUS:76249094935
SN - 0008-5472
VL - 70
SP - 1265
EP - 1274
JO - Cancer research
JF - Cancer research
IS - 3
ER -