Expression of Ha-ras oncogene product in rat gastrointestinal carcinomas induced by chemical carcinogens

The expression of Ha-ras oncogene product in rat gastrointestinal carcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 1, 2-dimethylhydrazine (DMH) was studied by Western blotting and immunohistochemistry using anti-Ha-ras p 21 oncoprotein antibody. In Western blotting, high levels of c-Ha-ras p 21 were found in serially transplantable rat duodenal carcinomas induced by MNNG and rat colon carcinomas induced by DMH. Immunohistochemically, c-Ha-ras p 21 immunoreactivity was detected in 3 (16.7%) of 17 MNNG-induced stomach carcinomas and in 21 (63.6%) of 33 DMH-induced colon carcinomas, respectively. In the colon carcinomas, c-Ha-ras p 21 immunoreactivity in deeply invasive tumors was stronger than that in superficially invasive tumors and was expressed in all subserosal tumors. Moreover, all of the metastatic colon carcinomas had c-Ha-ras p 21 immunoreactive tumor cells. These findings suggest that c-Ha-ras p 21 expression plays an important role in tumor proliferation, invasion and metastasis of DMH-induced colon carcinoma.