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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2008) 32, 1302–1309 (Printed in Great Britain)
Interaction of p14ARF with Brca1 in cancer cell lines and primary breast cancer
Lizhi Heab, Catherine Fanab, Xiaoming Ningc, Xinchang Fengab, Yun Liud, Biao Chenab and Damu Tangab*
aDivision of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada
bFather Sean O'Sullivan Research Institute, St. Joseph's Hospital, Hamilton, ON, Canada
cLaboratory of Pathology, Heilongjiang Tumor Hospital, Harbin Medical University, Heilongjiang, PR China
dLaboratory of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Heilongjiang, PR China


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 1β 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.

Key words: p14ARF, Brca1, Prostate cancer, Breast cancer.

*Corresponding author. T3310, St. Joseph's Hospital, 50 Charlton Ave East, Hamilton, ON, L8N 4A6 Canada. Tel.: +1 905 522 1155x35168; fax: +1 905 540 6549.

Received 9 March 2008/24 April 2008; accepted 15 July 2008


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)