Document Detail


RhoA-dependent murine prostate cancer cell proliferation and apoptosis: role of protein kinase Czeta.
MedLine Citation:
PMID:  11980660     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously showed that RhoA played an important role in the proliferation of murine We prostate cancer (TRAMP) cells (P. M. Ghosh et al., Oncogene, 18: 4120-4130, 1999). Untransfected TRAMP cells as well as those expressing constitutively active RhoA (Q63L) mutant protein (Q63L cells) were highly proliferative. In contrast, TRAMP cells expressing dominant-negative RhoA (T19N) mutant protein (T19N cells) were slow growing. In this study, we showed, in addition, that T19N cells displayed reduced rates of apoptotic cell death in response to serum deprivation, compared with TRAMP and Q63L cells, and we studied the mechanisms of the effects of RhoA on TRAMP cell proliferation and apoptosis. Both proliferation and apoptosis of TRAMP and Q63L cells were dependent on the activation of phosphatidylinositol 3-kinase (PI3K). The ubiquitous mitogen-activated Ser/Thr kinase, p70S6 kinase, a downstream effector of PI3K, was overexpressed in TRAMP and Q63L cells. Another PI3K effector, the cell survival protein Akt, displayed increased activity in T19N cells, which did not express active RhoA, compared with TRAMP and Q63L cells. The atypical protein kinase C (PKC) isoform PKCzeta, which is downstream of PI3K, was activated in cells expressing active RhoA. In addition, expression of constitutively activated PKCzeta in TRAMP cells enhanced proliferation and p70S6 kinase phosphorylation, whereas the inhibition of PKCzeta activation resulted in activation of Akt and enhanced cell survival. Thus, the effects of RhoA on TRAMP cell proliferation and apoptosis may be mediated by PKCzeta.
Authors:
Paramita M Ghosh; Roble Bedolla; Margharita Mikhailova; Jeffrey I Kreisberg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  62     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-04-30     Completed Date:  2002-05-31     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2630-6     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Texas Health Science Center, San Antonio, Texas, USA. ghosh@uthscsa.edu
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Animals
Apoptosis / physiology
Cell Division / physiology
Cell Survival / physiology
Enzyme Activation
Male
Mice
Mice, Transgenic
Phosphorylation
Prostatic Neoplasms / enzymology*,  pathology*
Protein Kinase C / antagonists & inhibitors,  metabolism,  physiology*
Protein-Serine-Threonine Kinases*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Ribosomal Protein S6 Kinases / biosynthesis,  metabolism
rhoA GTP-Binding Protein / antagonists & inhibitors,  biosynthesis,  physiology*
Grant Support
ID/Acronym/Agency:
2T32HL07446-16/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases; EC 2.7.11.1/protein kinase C zeta; EC 2.7.11.13/Protein Kinase C; EC 3.6.5.2/rhoA GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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