A genetic model for undifferentiated cell tumor formation: similar tumors formed by different cell lines transformed by the EIA oncogene

Abstract

The activation of oncogenes and the mutation/deletion of supressor genes may be involved in tumor heterogeneity. In an attempt to study tumor heterogeneity, we transformed cell lines from epithelial (PAM 212), mesenchymal (NIH-3T3), or melanocytic origin (L-BIOBR) with the wild type Ela oncogene. To make the cell lines tumorigenic, cells were infected with Harvey sarcoma virus carrying the v-H-ras oncogene. The transformed cells were injected into nude mice and the tumors studied by optical and electron microscopy. The tumors formed by v-H-ras-transformed cells consisted of epitheliod melanomas, spindle cells sarcomas and poorly-differentiated carcinomas, depending on the cell of origin. In contrast, the tumors obtained from cells also carrying the Ela oncogene showed a predominant small and undifferentiated cell pattem regardless of the cell of origin. We conclude that the Ela oncogene products induce a negative control of differentiation, independent of the cell type, and that tumors formed by cells carrying the Ela oncogene display an undifferentiated cell pattem.