S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Attenuation of transforming growth factor beta-induced growth inhibition in human hepatocellular carcinoma cell lines by cyclin D1 overexpression
- Jong, Hyun-Soon; Lee, Ho Soon; Kim, Tae You; Im, Young-Hyuck; Park, Jae-Won; Kim, Noe Kyeong; Bang, Yung-Jue
- Issue Date
- Biochem. Biophys. Res. Commun. 292, 383-389
- Carcinoma, Hepatocellular/*genetics/metabolism/pathology; Cell Cycle; Cell Division/drug effects; Cyclin D1/biosynthesis/*genetics; DNA/biosynthesis; DNA, Antisense/pharmacology; Gene Amplification; Growth Inhibitors/*antagonists & inhibitors; Liver Neoplasms/*genetics/metabolism/pathology; RNA, Neoplasm/biosynthesis; Receptors, Transforming Growth Factor beta/biosynthesis/genetics; Transcriptional Activation; Transfection; Transforming Growth Factor beta/*antagonists & inhibitors; Tumor Cells, Cultured
- Transforming growth factor-beta1 (TGF-beta1) causes growth inhibition in many cell types. Since its role in the outgrowth of human hepatocellular carcinoma (HCC) is not clearly understood, we investigated the growth inhibitory effects of TGF-beta1, the genetic and molecular integrity of TGF-beta receptors, and the expression levels of cell cycle regulating proteins in 11 human HCC cell lines. Of 11 cell lines, 3 (27%) showed growth inhibition to TGF-beta1, whereas the other 8 cell lines did not. We performed Southern and Northern analysis of TGF-beta type I and II receptors and examined poly-adenine track mutation of the TGF-beta type II receptor, but failed to find any genetic mutation. The transcriptional induction of plasminogen activator inhibitor-1 and p21(WAF1/CIP1) by TGF-beta were detected in all HCC cell lines, implying that the molecular integrity of the TGF-beta receptors might be intact. The amplification and overexpression of cyclin D1 gene was detected in 4 (50%) of 8 HCC cells that showed resistance to TGF-beta1. The suppression of cyclin D1 expression with antisense cyclin D1 facilitated the TGF-beta1-triggered growth inhibition in a TGF-beta1 resistant HCC cell line containing amplified cyclin D1 gene. In conclusion, the overexpression of cyclin D1 may be responsible for the attenuation of TGF-beta1 induced growth inhibition in some HCC cells.
- 0006-291X (Print)
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