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Cell Growth & Differentiation, Vol 7, Issue 12 1705-1712, Copyright © 1996 by American Association of Cancer Research


ARTICLES

p21ras-mediated decrease of the retinoblastoma protein in fibroblasts occurs through growth factor-dependent mechanisms

L Klvinen, E Tiihonen, T Haapajarvi and M Laiho
Haartman Institute, Department of Virology, University of Helsinki, Finland.

Stable coexpression of the human retinoblastoma protein (pRB) cDNA and EJ c-Ha-ras oncogene in murine fibroblasts leads to loss of pRB expression with concomitant transformation of the cells (1). We show here that conditional expression of p21ras in mouse fibroblasts expressing human pRB leads to a rapid decrease of pRB expression at both protein and mRNA levels. The decrease of pRB mRNA is blocked by cycloheximide, suggesting the requirement of ongoing protein synthesis. p21ras expression leads also to decreases of c-myc and tissue metalloproteinase inhibitor-2 mRNAs, whereas cyclin-dependent kinase 4, cyclin D1, E2F-1, and ornithine decarboxylase are unaffected. The decrease in pRB is accompanied by progressive morphological transformation of the cells. The effect of p21ras on pRB expression was serum and growth factor dependent. A shift of the cells to low serum (0.2% FCS) abolished the effects of p21ras on pRB, but this effect was reconstituted by the addition of growth factors epidermal growth factor, fibroblast growth factor-2, transforming growth factor beta 1, and platelet-derived growth factor to the cells. The results suggest a complex interaction between p21ras, pRB, and growth factors in the control of cell growth. p21ras appears to drive the cell cycle by deregulation of key cell cycle regulators, the functions of which in low serum become redundant or require the presence of growth factors positively driving the cell cycle.


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L. Kivinen and M. Laiho
Ras- and Mitogen-activated Protein Kinase Kinase-dependent and -independent Pathways in p21Cip1/Waf1 Induction by Fibroblast Growth Factor-2, Platelet-derived Growth Factor, and Transforming Growth Factor-{beta}1
Cell Growth Differ., September 1, 1999; 10(9): 621 - 628.
[Abstract] [Full Text]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1996 by the American Association of Cancer Research.