S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
p130 mediates TGF-beta-induced cell-cycle arrest in Rb mutant HT-3 cells
- Choi, Hyun Ho; Jong, Hyun Soon; Song, Sang Hyun; Kim, Tae You; Kim, Noe Kyeong; Bang, Yung Jue
- Issue Date
- Gynecol Oncol 2002;86:184-9
- Blood Proteins/*metabolism; Cell Cycle/genetics; Down-Regulation; Gene Expression Regulation, Neoplastic; Genes, Retinoblastoma/*genetics; Growth Inhibitors/*metabolism; *Mutation; *Proteins; Retinoblastoma-Like Protein p130; Transforming Growth Factor beta/*metabolism; Tumor Cells, Cultured; Uterine Cervical Neoplasms/*metabolism
- 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 E2F-4/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(1) phase. p21 protein level was elevated in TGF-beta-treated HT-3 cells, while other G(1) 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.
- 0090-8258 (Print)
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