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 b een suggested from in vitro studies to be partly regulated by the onco gene products, c-Jun and c-Fos, their distributions were compared in n ormal rat tissues and preneoplastic hepatic lesions induced by the Sol t-Farber protocol. Immunohistochemically demonstrated GST-P protein wa s positively correlated with expression of both c-Jun and c-Fos in the epidermis of the skin and the smooth muscle of adult lung and with ei ther c-Jun or c-Fos respectively in the bile ducts and bronchial epith elium. However, GST-P expression was also observed in proximal and dis tal straight segments of the kidney and other tissues negative for c-J un and c-Fos and both c-Jun and c-Fos were present in the renal proxim al and distal convoluted tubules, where GST-P was lacking. Thus, the l ocalization of GST-P was in some cases clearly separable from those of c-Jun or c-Fos. GST-P was found to be focally expressed from an early stage of hepatocarcinogenesis, when c-Jun was not detectable. At late r stages, this oncogene product was stained in 35.7% of GST-P-positive foci, with a clear relation to the degree of GST-P staining. Since GS T-P is not always accompanied by appreciable c-Jun or c-Fos, these onc ogene products are apparently not prerequisites for its expression. Ho wever, c-Jun may be partly responsible for maintaining high levels of GST-P in hepatic foci at later stages of hepatocarcinogenesis.