Atypical PKCiota Contributes to Poor Prognosis Through Loss of Apical-basal Polarity and Cyclin E Overexpression in Ovarian Cancer

Author(s)

Astrid M. Eder, University of Texas M.D. Anderson Cancer Center
Xiaomei Sui, University of Texas M.D. Anderson Cancer Center
Daniel G. Rosen, University of Texas M.D. Anderson Cancer Center
Laura K. Nolden, University of Texas M.D. Anderson Cancer Center
Kwai Wa Cheng, University of Texas M.D. Anderson Cancer Center
John P. Lahad, University of Texas M.D. Anderson Cancer Center
Madhuri Kango-Singh, University of DaytonFollow
Karen H. Lu, University of Texas M.D. Anderson Cancer Center
Carla L. Warneke, University of Texas M.D. Anderson Cancer Center
Edward N. Atkinson, University of Texas M.D. Anderson Cancer Center
Isabelle Bedrosian, University of Texas M.D. Anderson Cancer Center
Khandan Keyomarsi, University of Texas M.D. Anderson Cancer Center
Wen-lin Kuo, Lawrence Berkeley National Laboratory
Joe W. Gray, Lawrence Berkeley National Laboratory
Jerry C. P. Yin, University of Wisconsin-Madison
Jinsong Liu, University of Texas M.D. Anderson Cancer Center
Georg Halder, University of Texas M.D. Anderson Cancer Center
Gordon B. Mills, University of Texas M.D. Anderson Cancer Center

Document Type

Article

Publication Date

8-30-2005

Publication Source

Proceedings of the National Academy of Sciences of the United States of America

Abstract

We show that atypical PKCι, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCι protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCι DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCι proteins levels are associated with increased Cyclin E protein expression and proliferation in ovarian cancers. In nonserous ovarian cancers, increased PKCι protein levels, particularly in the presence of Cyclin E, are associated with markedly decreased overall survival. These results implicate PKCι as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKCι is a novel target for therapy.

Inclusive pages

12519-12524

ISBN/ISSN

0027-8424

Document Version

Published Version

Comments

This document has been made available for download in accordance with the publisher's policy on self-archiving. It is freely available online through the PNAS open access option.

Permission documentation on file.

Copyright

Copyright © 2005, National Academy of Sciences

Publisher

National Academy of Sciences

Volume

102

Peer Reviewed

yes

Issue

35

eCommons Citation

Eder, Astrid M.; Sui, Xiaomei; Rosen, Daniel G.; Nolden, Laura K.; Cheng, Kwai Wa; Lahad, John P.; Kango-Singh, Madhuri; Lu, Karen H.; Warneke, Carla L.; Atkinson, Edward N.; Bedrosian, Isabelle; Keyomarsi, Khandan; Kuo, Wen-lin; Gray, Joe W.; Yin, Jerry C. P.; Liu, Jinsong; Halder, Georg; and Mills, Gordon B., "Atypical PKCiota Contributes to Poor Prognosis Through Loss of Apical-basal Polarity and Cyclin E Overexpression in Ovarian Cancer" (2005). Biology Faculty Publications. 228.
https://ecommons.udayton.edu/bio_fac_pub/228