Atypical PKCι contributes to poor prognosis through loss of apical-basal polarity and Cyclin E overexpression in ovarian cancer

Astrid M. Eder, Xiaomei Sui, Daniel G. Rosen, Laura K. Nolden, Kwai Wa Cheng, John P. Lahad, Madhuri Kango-Singh, Karen H. Lu, Carla L. Warneke, Edward M. Atkinson, Isabelle Bedrosian, Khandan Keyomarsi, Wen Lin Kuo, Joe W. Gray, Jerry C.P. Yin, Jinsong Liu, Georg Halder, Gordon B. Mills

Research output: Contribution to journalArticle

195 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12519-12524
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number35
DOIs
StatePublished - Aug 30 2005

Keywords

  • Epithelial cell polarity
  • Proliferation

ASJC Scopus subject areas

  • General

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    Eder, A. M., Sui, X., Rosen, D. G., Nolden, L. K., Cheng, K. W., Lahad, J. P., Kango-Singh, M., Lu, K. H., Warneke, C. L., Atkinson, E. M., Bedrosian, I., Keyomarsi, K., Kuo, W. L., Gray, J. W., Yin, J. C. P., Liu, J., Halder, G., & Mills, G. B. (2005). Atypical PKCι contributes to poor prognosis through loss of apical-basal polarity and Cyclin E overexpression in ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America, 102(35), 12519-12524. https://doi.org/10.1073/pnas.0505641102