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

Abstract

Cell growth regulation is a highly complex process. The present study demonstrates a novel link between alterations in insulin-mediated regulation during malignant conversion and the expression of S-adenosylmethionine decarboxylase, a key regulatory activity in the biosynthesis of polyamines. H-ras transformed mouse 10 T 1/2 cell lines exhibiting increasing malignant potential were investigated for possible insulin-mediated changes in S-adenosylmethionine decarboxylase gene expression. Selective induction of S-adenosylmethionine decarboxylase gene expression was observed, because, in contrast to nontransformed 10T 1/2 cells, only H-ras transformed cells capable of only benign tumour formation or H-ras transformed metastatic cells exhibited marked elevations in S-adenosylmethionine decarboxylase mRNA levels. Evidence for regulation of S-adenosylmethionine decarboxylase gene expression at both transcriptional and post-transcriptional levels was found. Evidence was also found for a cycloheximide sensitive regulator of S-adenosylmethionine decarboxylase gene expression in H-ras transformed metastatic cells, whose effect, in combination with insulin, resulted in a further augmentation of S-adenosylmethionine decarboxylase gene expression. This regulation was not present in H-ras transformed cells capable of only benign tumour formation. These results suggest that insulin can modulate S-adenosylmethionine decarboxylase gene expression in H-ras transformed cells and further suggests a mechanism of insulin stimulation of transformed cells wherein alterations in the regulatory activity of S-adenosylmethionine decarboxylase gene expression are critical and constitutes a part of an altered growth regulatory program associated with cellular transformation.