Liver Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 2003; 9(8): 1689-1696
Published online Aug 15, 2003. doi: 10.3748/wjg.v9.i8.1689
S-phase delay in human hepatocellular carcinoma cells induced by overexpression of integrin β1
Yu-Long Liang, Ting-Wen Lei, Heng Wu, Jian-Min Su, Li-Ying Wang, Qun-Ying Lei, Xi-Liang Zha
Yu-Long Liang, Heng Wu, Li-Ying Wang, Qun-Ying Lei, Xi-Liang Zha, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Ting-Wen Lei, Department of Biochemistry, Guiyang Medical College, Guiyang 550004, Guizhou Province, China
Jian-Min Su, Department of Chemistry, Shanghai Medical College, Fudan University, Shanghai 200032, China
Author contributions: All authors contributed equally to the work.
Supported by Grants from the National Natural Science Foundation of China, No.30000083 and Shanghai Municipal Government Science and Technology Committee, No.00JC14042
Correspondence to: Dr. Xi-Liang Zha, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, China. xlzha@shmu.edu.cn
Telephone: +86-21-54237696 Fax: +86-21-64179832
Received: March 5, 2003
Revised: March 19, 2003
Accepted: April 1, 2003
Published online: August 15, 2003
Abstract

AIM: To clarify the mechanisms of integrin overexpression in negatively regulating the cell cycle control of hepatocellular carcinoma cells SMMC-7721.

METHODS: The cell cycle pattern was determined by flow cytometry. The mRNA and protein expression levels were assayed by RT-PCR and Western blot, respectively. Stable transfection was performed by Lipofectamine 2000 reagent, and cells were screened by G418.

RESULTS: Overexpression of α5β1 or β1 integrin induced S-phase delay in SMMC-7721 cells, and this delay was possibly due to the accumulation of cyclin-dependent kinase inhibitors (CKIs) p21cip1 and p27kip1. The decrease of protein kinase B (PKB) phosphorylation was present in this signaling pathway, but focal adhesion kinase (FAK) was not involved. When phosphorylation of PKB was solely blocked by wortmannin, p27kip1 protein level was increased. Moreover, S-phase delay was recurred when attachment of the parental SMMC-7721 cells was inhibited by the preparation of poly-HEME, and this cell cycle pattern was similar to that of β1-7721 or α5β1-7721 cells.

CONCLUSION: S-phase delay induced by overexpression of integrin β1 subunit is attributed to the decrease of PKB phosphorylation and subsequent increases of p21cip1 and p27kip1 proteins, and may be involved in the unoccupied α5β1 because of lack of its ligands.

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