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Title: Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer
Authors: 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
Mills, Gordon B # ×
Issue Date: Aug-2005
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:102 issue:35 pages:12519-24
Abstract: We show that atypical PKCiota, 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, PKCiota protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCiota 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 PKCiota proteins levels are associated with increased Cyclin E protein expression and proliferation in ovarian cancers. In nonserous ovarian cancers, increased PKCiota protein levels, particularly in the presence of Cyclin E, are associated with markedly decreased overall survival. These results implicate PKCiota as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKCiota is a novel target for therapy.
URI: 
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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