EXPRESSION OF THE ERB B-ONCOGENE IN THE MORRIS HEPATOMA-7777

Altered expression of protooncogenes/oncogenes is believed to be invol ved in hepatocarcinogenesis of the chemically induced, transplantable Morris hepatoma 7777. We compared the mRNA expression of c-N-ras and v -erb B mRNA of normal rat liver with that of Morris hepatoma 7777 usin g Northern blot analysis and in situ hybridization. Northern blot anal ysis revealed a strong overexpression of the v-erb B related mRNA, whi le the c-N-ras mRNA was only slightly increased. In situ hybridization using a c-N-ras mRNA probe also showed only a slighly increased numbe r of silver grains in the hepatoma cells compared with normal rat live r On the other hand, the v-erb B related mRNA was strongly overexpress ed in the hepatoma cells, while the connective-tissue capsule, the blo od vessels, blood cells and the necrotic foci did not show an elevated v-erb B related gene mRNA expression. Similar results were obtained i n liver metastases. The detectable v-erb B hybridization signal was lo st by pretreatment with RNase A. We conlcude that the c-N-ras gene is of minor importance in the chemically induced, transplantable Morris h epatoma 7777, while the increased expression of the v-erb B related mR NA is due to a selection of ligand-independent tyrosine kinase activit y.