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Basic fibroblast growth factor selectively regulates ornithine decarboxylase gene expression in malignant H‐ ras transformed cells
Author(s) -
Hurta Robert A.R.,
Huang Aiping,
Wright Jim A.
Publication year - 1996
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19960315)60:4<572::aid-jcb13>3.0.co;2-j
Subject(s) - ornithine decarboxylase , ornithine decarboxylase antizyme , basic fibroblast growth factor , biology , gene expression , cycloheximide , carboxy lyases , microbiology and biotechnology , fibroblast , cell culture , biochemistry , protein biosynthesis , gene , enzyme , growth factor , genetics , receptor
Cell growth regulation by fibroblast growth factors (FGFs) is highly complex. The present study demonstrates a novel link between alterations in bFGF regulation during malignant conversion and the expression of ornithine decarboxylase, a key rate‐limiting and regulatory activity in the biosynthesis of polyamines. H‐ ras transformed mouse 10T½ cell lines exhibiting increasing malignant potential were investigated for possible bFGF‐mediated changes in ornithine decarboxylase gene expression. Selective induction of ornithine decarboxylase gene expression was observed, since, in contrast to nontransformed 10T½ cells and cells capable of only benign tumor formation, H‐ ras transformed metastatic cells exhibited marked elevations in ornithine decarboxylase message levels. Evidence for regulation of ornithine decarboxylase gene expression by bFGF at both transcription and posttranscription was found. Actinomycin D pretreatment of malignant cells prior to bFGF exposure inhibited the increase in ornithine decarboxylase message. Furthermore, striking differences in the rates of ornithine decarboxylase message decay were observed when cells treated with bFGF were compared to untreated control cells, with the half‐life of ornithine decarboxylase mRNA increasing from 2.4 h in untreated cells to 12.5 h in cells exposed to bFGF. Evidence was also obtained for a cycloheximide‐sensitive regulator of ornithine decarboxylase gene expression whose effect, in combination with bFGF, resulted in a further augmentation of ornithine decarboxylase gene expression. Furthermore, evidence is presented to suggest a possible role for G‐protein‐coupled events in the bFGF‐mediated regulation of ornithine decarboxylase gene expression. The bFGF regulation of ornithine decarboxylase expression in H‐ ras transformed malignant cells appeared to occur independent of protein kinase C‐mediated events. These results show that bFGF can modulate ornithine decarboxylase gene expression in malignant H‐ ras transformed cells and further suggests a mechanism of growth factor stimulation of malignant cells wherein early alterations in the regulatory control of ornithine decarboxylase gene expression are critical. © 1996 Wiley‐Liss, Inc.