ADENOVIRUS ELA-MEDIATED TUMOR SUPPRESSION BY A C-ERBB-2 NEU-INDEPENDENT MECHANISM/

We reported previously that the adenovirus E1a gene reversed the trans formed phenotype of one human melanoma and one fibrosarcoma cell line (S. Frisch, Proc, Natl, Acad, Sci, USA, 88: 9077-9081, 1991). To deter mine the generality of the tumor suppression effects of E1a, a diversi ty of tumor cell lines, including A204 rhabdomyosarcoma, RD rhabdomyos arcoma, Saos-2 osteosarcoma, NCI-H23 non-small cell lung carcinoma, MD A-MB435S breast carcinoma, and ras-transformed MDCK kidney epithelial cells, were infected with a retrovirus bearing the 125 E1a coding sequ ence, We demonstrate here that the expression of E1a severely reduced the anchorage-independent and tumorigenic growth of these cell lines w ithout affecting their growth under normal culture conditions, The par ental tumor cells used in this study did not overexpress c-erbB-2/neu, and E1a did not affect its expression in these cells, Thus, tumor sup pression by E1a can operate in a wide variety of human tumor cells by c-erbB-2/neu-independent mechanisms. E1a also sensitized these cell li nes to the cytotoxic effects of the anticancer drugs etoposide and cis platin, The results suggest that E1a could prove useful for the gene t herapy of a wide variety of human cancers.