Signal Transduction Involved in Cell Cycle Regulation of Normal Hepatocyte and Hepatoma Cells

作者: Yutaka Sasaki , Masayoshi Horimoto , Norio Hayashi

DOI: 10.1007/978-4-431-67887-8_6

关键词: ChemistryCell cycleCyclin-dependent kinaseMAPK cascadeGrowth factor receptorSignal transductionHepatocyte growth factorCell growthMAPK/ERK pathwayCell biology

摘要: The cell cycle is controlled by cyclin/cyclin-dependent kinase (CDK) complexes and CDK inhibitors. expression function of these molecules are induced modulated signal transduction governing growth differentiation. We found that when normal rat hepatocyte was factor (HGF), HGF receptor (MET) activated, with association MET receptor-bound protein (GRB)-2, which the initial step activation mitogen-activated (MAPK) cascade. also report MAPK cascade sequentially followed growth. Before density reached confluence, p21/WAF1, a inhibitor, prevented Cdk4 activity, resulting in arrest. Thus, growth, strictly controlled. In contrast, human hepatocellular carcinomas (HCCs), MAPK/ERK (extracellular regulated kinase) constitutively upregulated. Enhanced GRB-2 receptors or S0S, ras activator, observed, may account for activation. On other hand, p21/WAF1 HCCs deficient overwhelmed CDKs excess stoichiometry. These observations indicate active and/or disturbance regulators contributes much to unrestricted HCCs. Finally, we introduced deletion mutants into HepG2 cells, reduction activity prevention addition, vector arrested at G1/S transition inhibition results provide new strategy anticancer therapy modulating machinery.

参考文章(30)
M Shiohara, WS el-Deiry, M Wada, T Nakamaki, S Takeuchi, R Yang, DL Chen, B Vogelstein, HP Koeffler, Absence of WAF1 Mutations in a Variety of Human Malignancies Blood. ,vol. 84, pp. 3781- 3784 ,(1994) , 10.1182/BLOOD.V84.11.3781.BLOODJOURNAL84113781
Truss M, Beato M, Müller R, Herber B, Inducible regulatory elements in the human cyclin D1 promoter. Oncogene. ,vol. 9, pp. 1295- 1304 ,(1994)
Masahiro Amenomori, Ryuichi Kita, Toshiki Komeda, Mituo Ikenaga, Takehiro Sando, Motonobu Furukawa, Kazuwa Nakao, Naoshi Nishida, Icho Shibagaki, Kanji Ishizaki, Yoshihiro Fukuda, Amplification and Overexpression of the Cyclin D1 Gene in Aggressive Human Hepatocellular Carcinoma Cancer Research. ,vol. 54, pp. 3107- 3110 ,(1994)
A Seth, F.A. Gonzalez, S Gupta, D.L. Raden, R.J. Davis, Signal transduction within the nucleus by mitogen-activated protein kinase. Journal of Biological Chemistry. ,vol. 267, pp. 24796- 24804 ,(1992) , 10.1016/S0021-9258(18)35834-4
Alain Puisieux, Katherine Galvin, Frederic Troalen, Brigitte Bressac, Christophe Marcais, Eithan Galun, Frederique Ponchel, Cengiz Yakicier, Jingwei Ji, Mehmet Ozturk, Retinoblastoma and p53 tumor suppressor genes in human hepatoma cell lines. The FASEB Journal. ,vol. 7, pp. 1407- 1413 ,(1993) , 10.1096/FASEBJ.7.14.8224613
R H Chen, C Sarnecki, J Blenis, Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Molecular and Cellular Biology. ,vol. 12, pp. 915- 927 ,(1992) , 10.1128/MCB.12.3.915
Sean E. Egan, Barton W. Giddings, Mary W. Brooks, László Buday, Andrew M. Sizeland, Robert A. Weinberg, Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation Nature. ,vol. 363, pp. 45- 51 ,(1993) , 10.1038/363045A0
Givol D, Pierce Jh, Chedid M, Lin D, Mercer We, Michieli P, Induction of WAF1/CIP1 by a p53-independent Pathway Cancer Research. ,vol. 54, pp. 3391- 3395 ,(1994)
Sally Cowley, Hugh Paterson, Pauline Kemp, Christopher J Marshall, Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells Cell. ,vol. 77, pp. 841- 852 ,(1994) , 10.1016/0092-8674(94)90133-3
Tony Hunter, Jonathan Pines, Cyclins and cancer II: Cyclin D and CDK inhibitors come of age Cell. ,vol. 79, pp. 573- 582 ,(1994) , 10.1016/0092-8674(94)90543-6