title: Interaction of p14ARF with Brca1 in cancer cell lines and primary breast cancer.
abstract: We report an association between p14ARF and Brca1 in which both proteins co-immunoprecipitate (co-IP) in DU145 cells. The N-terminal 64 residues of p14ARF encoded by exon 1beta are sufficient for this association. Inside the cell, ectopic p14ARF co-localizes with ectopic and endogenous Brca1 in A375 cells. Endogenous p14ARF co-localizes with endogenous Brca1 in DU145 cells but not in H1299 cells. Since p14ARF interacts with B23 in the nucleolus, Brca1 co-localizes with B23 in DU145 but not in H1299 cells. While ectopic ARF potently inhibited DU145 cell proliferation, it had no effect on the proliferation of H1299 cells, suggesting that the interaction between ARF and Brca1 contributes to ARF-mediated tumor suppression. Consistent with this notion, ectopic p14ARF modulates endogenous Brca1 expression in MCF7 breast cancer cells and p14ARF co-localizes with Brca1 in normal breast epithelial cells. This co-localization is enhanced in primary breast cancer. Taken together, the results show that p14ARF associates with Brca1, which may play a major role in tumor suppression.
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Lizhi
authors.initials: L
authors.lastname: He
authors.forename: Catherine
authors.initials: C
authors.lastname: Fan
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ning
authors.forename: Xinchang
authors.initials: X
authors.lastname: Feng
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Biao
authors.initials: B
authors.lastname: Chen
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008875:Middle Aged; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D025803:Tumor Suppressor Protein p14ARF; D020727:ADP-Ribosylation Factors