The activation of oncogenes and the mutation/deletion of suppressor 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 E1a 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 E1a oncogene showed a predominant small and undifferentiated cell pattern regardless of the cell of origin. We conclude that the E1a
oncogene products induce a negative control of differentiation, independent of the cell type, and that
tumors formed by cells carrying the E1a oncogene display an undifferentiated cell pattern.