cancer-associated PCNA expressed in breast cancer has implications as a potential biomarker

Two isoforms of proliferating cell nuclear antigen (PCNA) have been observed in breast cancer cells. Commercially available antibodies to PCNA recognize both isoforms and, therefore, cannot differentiate between the PCNA isoforms in malignant and nonmalignant breast epithelial cells and tissues. We...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 51; pp. 19472 - 19477
Main Authors: Malkas, Linda H, Herbert, Brittney Shea, Abdel-Aziz, Waleed, Dobrolecki, Lacey E, Liu, Yang, Agarwal, Beamon, Hoelz, Derek, Badve, Sunil, Schnaper, Lauren, Arnold, Randy J, Mechref, Yehia, Novotny, Milos V, Loehrer, Patrick, Goulet, Robert J, Hickey, Robert J
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 19-12-2006
National Acad Sciences
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Summary:Two isoforms of proliferating cell nuclear antigen (PCNA) have been observed in breast cancer cells. Commercially available antibodies to PCNA recognize both isoforms and, therefore, cannot differentiate between the PCNA isoforms in malignant and nonmalignant breast epithelial cells and tissues. We have developed a unique antibody that specifically detects a PCNA isoform (caPCNA) associated with breast cancer epithelial cells grown in culture and breast-tumor tissues. Immunostaining studies using this antibody suggest that the caPCNA isoform may be useful as a marker of breast cancer and that the caPCNA-specific antibody could potentially serve as a highly effective detector of malignancy. We also report here that the caPCNA isoform functions in breast cancer-cell DNA replication and interacts with DNA polymerase δ. Our studies indicate that the caPCNA isoform may be a previously uncharacterized detector of breast cancer.
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Author contributions: L.H.M. and R.J.H. designed research; B.S.H., B.A., D.H., W.A.-A., L.E.D., Y.L., S.B., and R.J.A. performed research; B.S.H., W.A.-A., D.H., and P.L. contributed new reagents/analytic tools; L.H.M., D.H., B.A., S.B., L.S., R.J.A., Y.M., M.V.N., and R.J.H. analyzed data; and L.H.M. and R.J.H. wrote the paper.
Communicated by Lawrence H. Einhorn, Indiana University, Indianapolis, IN, August 2, 2006
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0604614103