S-adenosylmethionine decarboxylase gene expression is regulated by the cAMP signal transduction pathway in H-ras transformed fibrosarcoma cells capable of malignant progression

Ichiro Sekiya, Peter Koopman, Kunikazu Tsuji, Sabine Mertin, Vincent Harley, Yoshihiko Yamada, Kenichi Shinomiya, Akira Niguji, Masaki Noda

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The hypothesis that H-ras transformed cells contain alterations in signalling pathways important in controlling the expression of S-adenosylmethionine decarboxylase, (SAMDC) a highly regulated activity in the biosynthesis of polyamines was tested. Mouse 10 T1/2 fibroblasts and H-ras transformed cell lines of varying degrees of malignant potential were treated with agents which affect cAMP levels within cells. Elevations in SAMDC expression were noted in H-ras transformed metastatic C3 cells, which were not observed in either parental, nontransformed 10 T1/2 fibroblast cells, or in ras transformed NR3 cells, which are only capable of benign tumour formation. Forskolin, a stimulator of cAMP synthesis, was able to increase SAMDC enzyme activity but the response which occurred was dependent upon the cellular phenotype expressed. Actinomycin D pre-treatment of C3 cells prior to exposure to forskolin did not abrogate the elevation observed in SAMDC gene expression suggesting that this was not a transcriptional process mediated event. Forskolin pre-treatment of C3 cells did result in a marked increase in the half-life of SAMDC mRNA transcripts suggesting a role for post-transcriptional stabilization. Furthermore, cycloheximide treatment of malignant C3 cells resulted in elevated SAMDC mRNA levels. Treatment of malignant C3 cells with both cycloheximide and forskolin together resulted in a further additive elevation in SAMDC message levels. Cycloheximide treatment alone was found to affect the half-life of SAMDC mRNA through a mechanism of post-transcriptional stabilization. Additionally, altered SAMDC gene expression in C3 cells which occurred in response to cAMP alterations, was enhanced by stimulation of a protein kinase C pathway suggesting possible interactions between protein kinase C- and cAMP-mediated pathways which affect the regulation of SAMDC expression in highly malignant C3 cells. These results demonstrate aberrant regulation of signalling pathways involved in controlling SAMDC gene expression in H-ras transformed cells capable of malignant progression and provide further insight into the altered growth regulatory program associated with H-ras mediated cellular transformation and malignant progression.

Original languageEnglish
Pages (from-to)209-221
Number of pages13
JournalJournal of Cellular Biochemistry
Issue numberSUPPL. 36
Publication statusPublished - 15 May 2001
Externally publishedYes


  • CAMP
  • H-ras
  • Malignant progression
  • S-adenosylmethionine decarboxylase

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