Cyclic AMP blocks expression of the c-sis gene in tumor cells.
Some human tumor cell lines express the c-sis gene, the proto-oncogene of the transforming gene v-sis, and produce platelet-derived growth factor, which may contribute to carcinogenesis by autocrine or paracrine mechanisms. Here we demonstrate that c-sis expression in some human glioma and osteosarcoma cell lines can be blocked by agents that increase cellular cyclic adenosine monophosphate (cAMP). Forskolin, 8-bromocyclic AMP, cholera toxin, and prostaglandin E1 reduced c-sis mRNA in these cells by up to 90%. c-sis transcription rates were reduced by agents that increase cAMP; the stability of c-sis mRNA was unaffected. The possible therapeutic value of blocking the expression of tumor growth factor genes pharmacologically warrants further study.
Harsh
G R
GR
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143-0724.
Kavanaugh
W M
WM
Starksen
N F
NF
Williams
L T
LT
D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D011519:Proto-Oncogenes; D011956:Receptors, Cell Surface / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D005576:Colforsin; D000242:Cyclic AMP; D017479:Receptors, Platelet-Derived Growth Factor