Insulin-mediated alterations in S-adenosylmethionine decarboxylase expression in H-ras transformed cells of varying degrees of malignancy

Cell growth regulation is a highly complex process. The present study demon strates a novel link between alterations in insulin-mediated regulation dur ing malignant conversion and the expression of S-adenosylmethionine decarbo xylase, a key regulatory activity in the biosynthesis of polyamines. H-ras transformed mouse 10 T 1/2 cell lines exhibiting increasing malignant poten tial were investigated for possible insulin-mediated changes in S-adenosylm ethionine decarboxylase gene expression. Selective induction of S-adenosylm ethionine decarboxylase gene expression was observed, because, in contrast to nontransformed 10T 1/2 cells, only H-ras transformed cells capable of on ly benign tumour formation or H-ras transformed metastatic cells exhibited marked elevations in S-adenosylmethionine decarboxylase mRNA levels. Eviden ce for regulation of S-adenosylmethionine decarboxylase gene expression at both transcriptional and post-transcriptional levels was found. Evidence wa s also found for a cycloheximide sensitive regulator of S-adenosylmethionin e decarboxylase gene expression in H-ras transformed metastatic cells, whos e effect, in combination with insulin, resulted in a further augmentation o f S-adenosylmethionine decarboxylase gene expression. This regulation was n ot present in H-ras transformed cells capable of only benign tumour formati on. These results suggest that insulin can modulate S-adenosylmethionine de carboxylase gene expression in H-ras transformed cells and further suggests a mechanism of insulin stimulation of transformed cells wherein alteration s in the regulatory activity of S-adenosylmethionine decarboxylase gene exp ression are critical and constitutes a part of an altered growth regulatory program associated with cellular transformation. (C) 2000 Elsevier Science Inc. All rights reserved.