Adenovirus E1a-mediated tumor suppression by a c-erbB-2/neu-independent mechanism.
We reported previously that the adenovirus E1a gene reversed the transformed phenotype of one human melanoma and one fibrosarcoma cell line (S. Frisch, Proc. Natl. Acad. Sci. USA, 88: 9077-9081, 1991). To determine the generality of the tumor suppression effects of E1a, a diversity of tumor cell lines, including A204 rhabdomyosarcoma, RD rhabdomyosarcoma, Saos-2 osteosarcoma, NCI-H23 non-small cell lung carcinoma, MDA-MB435S breast carcinoma, and ras-transformed MDCK kidney epithelial cells, were infected with a retrovirus bearing the 12S E1a coding sequence. We demonstrate here that the expression of E1a severely reduced the anchorage-independent and tumorigenic growth of these cell lines without affecting their growth under normal culture conditions. The parental 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 suppression by E1a can operate in a wide variety of human tumor cells by c-erbB-2/neu-independent mechanisms. E1a also sensitized these cell lines to the cytotoxic effects of the anticancer drugs etoposide and cisplatin. The results suggest that E1a could prove useful for the gene therapy of a wide variety of human cancers.
Frisch
S M
SM
La Jolla Cancer Research Foundation, California 92037, USA.
Dolter
K E
KE
D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018734:Genes, erbB-2; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D002945:Cisplatin; D005047:Etoposide; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C084301:E1A protein 243R, Human adenovirus type 5