Selective cytotoxic effect of tamoxifen on epithelial and fibroblastic cells transformed by different oncogenes.

To study the correlation between oncogenes and the cytotoxic effect of tamoxifen in estrogen negative (ER) cells, we transformed mouse keratinocyte and fibroblastic cell lines with several oncogenes and studied cell viability, thymidine incorporation and PKC levels. We show that v-myc and v-H-ras oncogenes increase sensitivity in both cell types and that Neu and mutant p53 also increase sensitivity to tamoxifen, more significantly in the epithelial cells. Conversely, transformation with adenovirus E1a oncogene induces resistance to tamoxifen in both cell types. These results indicate that tamoxifen may be effective in different kinds of malignant cells depending on the oncogenic alterations present in the cells.