Retinoic acid suppresses polyoma virus transformation by inhibiting transcription of the c-fos proto-oncogene.
In a previous paper, we predicted that retinoic acid suppressed polyoma virus transformation of rat F111 fibroblasts by affecting the expression of one or more genes that are involved in signalling pathways normally activated by the viral mT oncogene (Talmage & Lackey, Oncogene 7, 1837-1845, 1992). We had identified the cellular c-fos proto-oncogene as a possible candidate target for both polyoma virus mT and retinoic acid regulated expression. In this report we present the results of experiments that demonstrate that retinoic acid does indeed inhibit transcriptional transactivation of the c-fos promoter by polyoma virus, as well as by calf serum and purified serum growth factors. Further experiments demonstrate that inhibition of c-fos expression with antisense fos RNA also prevents polyoma virus induced transformation. Restoration of c-fos expression, even in the presence of retinoic acid, restored transformation, indicating that retinoic acid inhibition of c-fos expression is sufficient to explain the retinoid suppression of transformation. These results identify the c-fos proto-oncogene as a key nuclear target for mT-dependent transformation and show that the anticarcinogenic properties of retinoic acid can be brought about by inhibiting c-fos expression.
Talmage
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Institute of Human Nutrition, Columbia University, New York, NY 10032.
Listerud
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D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000187:drug effects*; D016762:Genes, fos; D011120:Polyomavirus / Q000187:drug effects* / Q000502:physiology; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D014212:Tretinoin