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 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.
Bielecki
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Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital and University of Toronto, 1-001, 38 Shuter St., East Annex, Ontario, M5B 1A6, Toronto, Canada.
Hurta
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D012437:Adenosylmethionine Decarboxylase / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002461:Cell Line, Transformed; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009374:Neoplasms, Experimental; D010641:Phenotype; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D007328:Insulin; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D003513:Cycloheximide; D012437:Adenosylmethionine Decarboxylase