Journal article
Expression of p66Shc protein correlates with proliferation of human prostate cancer cells
Oncogene, Vol.24(48), pp.7203-7212
2005
DOI: 10.1038/sj.onc.1208852
Abstract
p66Shc, an isoform of Shc adaptor proteins, is shown to mediate various signals, including cellular stress. However, little is known about its involvement in carcinogenesis. We previously showed that p66Shc protein level is upregulated by steroid hormones in human carcinoma cells and is higher in prostate cancer (PCa) specimens than adjacent noncancerous cells. In this study, we investigated the role of p66Shc protein in PCa cell proliferation. Among different PCa cell lines tested, p66Shc protein level showed positive correlation with cell proliferation, that is, rapid-growing cells expressed higher p66Shc protein than slow-growing cells. Exposure of slow-growing LNCaP C-33 cells to epidermal growth factor (EGF) and 5α-dihydrotestosterone (DHT) led to upregulation of proliferation and p66Shc protein level. Conversely, growth suppression of fast-growing cells by cellular form of prostatic acid phosphatase (cPAcP) expression, a negative growth regulator, downregulated their p66Shc protein level. Additionally, increased expression of p66Shc protein by cDNA transfection in LNCaP C-33 cells resulted in increased cell proliferation. Cell cycle analyses showed higher percentage of p66Shc-overexpressing cells at S phase (24%) than control cells (17%), correlating with their growth rates. On the other hand, transient knock-down of p66Shc expression by RNAi in rapidly growing cells decreased their proliferation as evidenced by the reduced cell growth as well as S phase in p66Shc-knocked down cells. The p66Shc signaling in cell growth regulation is apparently mediated by extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK). Thus, our results indicate a novel role for p66Shc in prostate carcinogenesis, in part, promoting cell proliferation.
Details
- Title: Subtitle
- Expression of p66Shc protein correlates with proliferation of human prostate cancer cells
- Creators
- Suresh Veeramani - University of Nebraska Medical CenterTsukasa Igawa - Nagasaki UniversityTa-Chun Yuan - University of Nebraska Medical CenterFen-Fen Lin - University of Nebraska Medical CenterMing-Shyue Lee - Georgetown UniversityJamie S Lin - University of Nebraska Medical CenterSonny L Johansson - University of Nebraska Medical CenterMing-Fong Lin - University of Nebraska Medical Center
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.24(48), pp.7203-7212
- Publisher
- Nature Publishing
- DOI
- 10.1038/sj.onc.1208852
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Language
- English
- Date published
- 2005
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359837302771
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