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p130 mediates TGF-β-induced cell-cycle arrest in Rb mutant HT-3 cells

Cited 9 time in Web of Science Cited 9 time in Scopus
Authors
Choi, Hyun Ho; Jong, Hyun-Soon; Song, Sang Hyun; Kim, Tae You; Kim, Noe Kyeong; Bang, Yung-Jue
Issue Date
2002-08
Publisher
Elsevier
Citation
Gynecologic Oncology, Vol.86 No.2, pp.184-189
Keywords
transforming growth factor-betaretinoblastoma protein familyp21cervical carcinoma
Abstract
Objective. The retinoblastoma proteins include Rb and the functionally and structurally related proteins p107 and p130. It has been reported that HT-3 cells are sensitive to TGF-beta growth inhibition, despite the Rb mutation. The purpose of this study was to elucidate the growth-inhibitory mechanism of TGF-beta in Rb mutant HT-3 cells. Methods. Growth inhibition by TGF-beta in cervical carcinoma cell lines was evaluated by counting cell numbers. Cell-cycle distribution was determined by staining DNA with propidium iodide (PI) and measured using a flow cytometer. The level of each protein expression was determined by Western blot analysis. To evaluate the assembly of cdk2/p21, cdk2/cyclin E, and E2174/p130 complexes by TGF-beta, immunoprecipitation was performed. Results. TGF-beta inhibited the proliferation of HT-3 cells expressing mutant Rb protein and efficiently induced cell-cycle arrest at G, phase. p21 protein level was elevated in TGF-beta-treated HT-3 cells, while other G, regulatory protein levels were unaltered. TGF-beta markedly enhanced the binding of p21 with cdk2 but decreased that of cdk2 with cyclin E and inhibited the phosphorylation of p130 but did not change Rb and p107 protein status. We also found that E2F-1 protein level was lower in TGF-beta-treated cells and suggest that this might be the result of enhanced binding between E2F-4 and p130. Conclusions. Our results demonstrate that p130, instead of Rb, can mediate growth inhibition by TGF-beta in Rb mutant HT-3 cells. (C) 2002 Elsevier Science (USA).
ISSN
0090-8258
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12144826

http://hdl.handle.net/10371/12138
DOI
https://doi.org/10.1006/gyno.2002.6740
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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