Genre
- Journal Article
Inhibition of DNA synthesis and cell proliferation is frequently lost during malignant transformation and occasionally, tumour cell proliferation is actually stimulated by transforming growth factor beta (1) (TGF-beta (1)). The present study demonstrates a novel link between alterations in TGF-beta (1) regulation during cellular transformation and malignant conversion and the expression of ornithine decarboxylase (ODC) which is a key rate limiting activity in the biosynthesis of polyamines and which is an enzyme that plays an important role in cell growth and differentiation. H-ras transformed mouse 10T1/2 cell lines of varying degrees of malignant potential were examined for possible TGF-beta (1)-mediated alterations in ODC expression. Selective induction of ODC gene expression occurred. This induction was dependent upon the cellular phenotype expressed and the mechanisms responsible for the regulation of the TGF-beta (1)-mediated alterations in ODC expression varied as a function of malignant potential. The TGF-beta (1)-mediated alterations in ODC gene expression involves de novo protein synthesis, transcriptional, and post-transcriptional events. Evidence is also presented to suggest a possible role for protein kinase C-mediated events, protein phosphatases, and G-protein-coupled events in the TGF-beta (1) mediated regulation of ODC expression in H-ras transformed cells. Evidence is also presented to suggest a possible role for cellular polyamines in the TGF-beta (1)-mediated alterations in ODC expression in H-ras transformed cells. Additionally, alterations in cellular polyamines were shown to influence TGF-beta (1) gene expression in H-ras transformed cells and that these alterations occurred, in part, through post-transcriptional events. The TGF-beta (1)-mediated regulation of ODC expression in H-ras transformed cells of varying degrees of malignant potential appears to be complex, multifaceted, and interactive. This study illustrates the importance of TGF-beta (1)-mediated regulation of ODC expression as a result of H-ras mediated cellular transformation and malignant progression, and further suggests that this TGF-beta (1)-mediated regulation constitutes an integral part of an altered growth regulatory program. (C) 2001 Wiley-Liss, Inc.
Univ Toronto, Dept Lab Med & Pathobiol, St Michaels Hosp, Toronto, ON M5B 1A6, Canada.; Hurta, RAR, Univ Toronto, Dept Lab Med & Pathobiol, St Michaels Hosp, 1-001,E Annex,38 Shuter St, Toronto, ON M5B 1A6, Canada.
NEW YORK; DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
WILEY-LISS
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Source type: Electronic(1)
Language
- English
Subjects
- MALIGNANT TRANSFORMATION
- malignant progression
- FACTOR-BETA
- 3'-UNTRANSLATED REGION
- METASTATIC PROGRESSION
- 3T3 FIBROBLASTS
- PROTEIN KINASE-C
- ornithine decarboxylase
- HUMAN-FIBROBLASTS
- cellular transformation
- Cell Biology
- MESSENGER-RNA
- Biochemistry & Molecular Biology
- altered regulation and expression
- MAMMALIAN RIBONUCLEOTIDE REDUCTASE
- DNA-SYNTHESIS
- TGF-beta 1