Genomic effects of the putative oncogene G alpha s. Chronic transcriptional activation of the c-fos proto-oncogene in endocrine cells - PubMed (original) (raw)

. 1994 Sep 9;269(36):22663-71.

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Genomic effects of the putative oncogene G alpha s. Chronic transcriptional activation of the c-fos proto-oncogene in endocrine cells

C Gaiddon et al. J Biol Chem. 1994.

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Abstract

Somatic mutations of the alpha subunit of Gs (G alpha s) have been detected in a variety of endocrine tumors. To test whether G alpha s is an oncogene, we investigated the genomic effects of G alpha s protein in which the GTPase activity had been inactivated. Results from transient transfection studies show that such proteins increase 1) transcription of a reporter gene driven by the minimal cAMP-responsive element (TGACGTCA) and 2) c-fos transcription in several endocrine cell lines (GH3, AtT20, and PC12). By promoter deletion analyses and genetic inactivation of cAMP-dependent protein kinase, we show that this transcriptional stimulation by G alpha s impinges on several regulatory elements within the c-fos promoter and operates within the protein kinase A pathways. Stable PC12 cell lines were established to analyze long-term effects of constitutively active G alpha s. Cell lines expressing mutated G alpha s have elevated cAMP levels and increased AP1 binding activity. Transcription of a variety of genes, including c-fos, c-jun, and junB, is increased in these cells. The strong and permanent effects of G alpha s on early immediate genes, and c-fos in particular, may be responsible for the oncogenic potential of G alpha s in endocrine cells.

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