Lack of correlated expression between the glutathione S-transferase P-form and the oncogene products c-Jun and c-Fos in rat tissues and preneoplastic hepatic foci

Since the expression of glutathione S-transferase P-form (GST-P)has been suggested from in vitro studies to be partly regulatedby the oncogene products, c-Jun and c-Fos, their distributionswere compared in normal rat tissues and preneoplastic hepaticlesions induced by the Solt—Farber protocol. Immunohistochemicallydemonstrated GST-P protein was positively correlated with expressionof both c-Jun and c-Fos in the epidermis of the skin and thesmooth muscle of adult lung and with either c-Jun or c-Fos respectivelyin the bile ducts and bronchial epithelium. However, GST-P expressionwas also observed in proximal and distal straight segments ofthe kidney and other tissues negative for c-Jun and c-Fos andboth c-Jun and c-Fos were present in the renal proximal anddistal convoluted tubules, where GST-P was lacking. Thus, thelocalization of GST-P was in some cases clearly separable fromthose of c-Jun or c-Fos. GST-P was found to be focally expressedfrom an early stage of hepatocarcinogenesis, when c-Jun wasnot detectable. At later stages, this oncogene product was stainedin 35.7% of GST-P-positive foci, with a clear relation to thedegree of GST-P staining. Since GST-P is not always accompaniedby appreciable c-Jun or c-Fos, these oncogene products are apparentlynot prerequisites for its expression. However, c-Jun may bepartly responsible for maintaining high levels of GST-P in hepaticfoci at later stages of hepatocarcinogenesis.