TY - JOUR
T1 - Expression of p66Shc protein correlates with proliferation of human prostate cancer cells
AU - Veeramani, Suresh
AU - Igawa, Tsukasa
AU - Yuan, Ta Chun
AU - Lin, Fen Fen
AU - Lee, Ming Shyue
AU - Lin, Jamie S.
AU - Johansson, Sonny L.
AU - Lin, Ming Fong
N1 - Funding Information:
We thank Dr Pier Giuseppe Pelicci at European Institute of Oncology (Milan, Italy) and Dr A Raymond Frackelton Jr at Brown University (Providence, RI) for the gift of the wild-type p66Shc cDNA; Dr Jin-Tang Dong at Emory University School of Medicine (Atlanta, GA) for TSU-Pr1 cell line. We thank Ms Jacquelynn Dahl’s help for screening p66Shc stable subclone cells. We also thank the supports from the core facilities, including Molecular Biology, DNA sequencing, Tissue Procurement and Flow Cytometry at UNMC. This study was supported in part by NIH grant CA88184, P20RR017675, P20RR018759, NCI P30 CA36727, Department of Defense PC040587 and PC05096, and the Graduate Student Fellowship of UNMC.
PY - 2005/11/3
Y1 - 2005/11/3
N2 - 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 p66 Shc protein level. Additionally, increased expression of p66 Shc 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.
AB - 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 p66 Shc protein level. Additionally, increased expression of p66 Shc 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.
KW - Cell proliferation
KW - Prostate cancer
KW - Prostatic acid phosphatase
KW - p66
UR - http://www.scopus.com/inward/record.url?scp=27944483366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27944483366&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208852
DO - 10.1038/sj.onc.1208852
M3 - Article
C2 - 16170380
AN - SCOPUS:27944483366
SN - 0950-9232
VL - 24
SP - 7203
EP - 7212
JO - Oncogene
JF - Oncogene
IS - 48
ER -