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Attenuation of transforming growth factor beta-induced growth inhibition in human hepatocellular carcinoma cell lines by cyclin D1 overexpression

Cited 20 time in Web of Science Cited 21 time in Scopus
Authors
Jong, Hyun-Soon; Lee, Ho Soon; Kim, Tae You; Im, Young-Hyuck; Park, Jae-Won; Kim, Noe Kyeong; Bang, Yung-Jue
Issue Date
2002
Publisher
Elsevier
Citation
Biochem. Biophys. Res. Commun. 292, 383-389
Keywords
Carcinoma, Hepatocellular/*genetics/metabolism/pathologyCell CycleCell Division/drug effectsCyclin D1/biosynthesis/*geneticsDNA/biosynthesisDNA, Antisense/pharmacologyGene AmplificationGrowth Inhibitors/*antagonists & inhibitorsLiver Neoplasms/*genetics/metabolism/pathologyRNA, Neoplasm/biosynthesisReceptors, Transforming Growth Factor beta/biosynthesis/geneticsTranscriptional ActivationTransfectionTransforming Growth Factor beta/*antagonists & inhibitorsTumor Cells, Cultured
Abstract
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.
ISSN
0006-291X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11906173

http://hdl.handle.net/10371/11867
DOI
https://doi.org/10.1006/bbrc.2002.6666
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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