title: RBCK1 drives breast cancer cell proliferation by promoting transcription of estrogen receptor alpha and cyclin B1.
abstract: Cell cycle regulatory pathways in breast cancer are incompletely described. Here, we report an important role in estrogen receptor alpha (ERalpha)-positive breast cancer cells for the protein kinase C1 (PKC1)-interacting protein RBCK1 in supporting cell cycle progression by driving transcription of ERalpha and cyclin B1. RBCK1-depleted cells exhibited increased accumulation in G(2)-M phase of the cell cycle, decreased proliferation, and reduced mRNA levels for ERalpha and its target genes cyclin D1 and c-myc. Chromatin immunoprecipitation revealed that ERalpha transcription is associated with RBCK1 recruitment to the ERalpha promoter, suggesting that transcriptional regulation is one mechanism by which RBCK1 affects ERalpha mRNA levels. G(2)-M phase arrest was mediated independently from reduced ERalpha levels, instead associated with transcriptional inhibition of the key G(2)-M regulator cyclin B1. In breast tumor samples, there was a positive correlation between levels of RBCK1, ERalpha, and cyclin B1 mRNA levels. Our findings suggest that RBCK1 regulates cell cycle progression and proliferation of ERalpha-positive breast cancer cells by supporting transcription of ERalpha and cyclin B1.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institute, Novum, S-141 57 Huddinge, Sweden. nina.gustafsson@ki.se
authors.forename: Nina
authors.initials: N
authors.lastname: Gustafsson
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhao
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Karin
authors.initials: K
authors.lastname: Dahlman-Wright
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D056744:Cyclin B1 / Q000235:genetics* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016193:G1 Phase; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D016192:Resting Phase, Cell Cycle; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases
chemical_list: D056744:Cyclin B1; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D014157:Transcription Factors; C504507:RBCK1 protein, human; D044767:Ubiquitin-Protein Ligases