Alteration of jun proto-oncogene status by plasmid transfection affects growth of human ovarian cancer cells

The AP-1 transcription factor (the Jun and Fos proteins) is suspected of pl aying an important role in the biology of human cancer. Human epithelial ov arian tumors and cancer cell lines express the c-jun and jun-B proto-oncoge nes at a high level, in contrast with the jun-D gene, We have investigated here the functional relevance of these observations for the growth of ovari an cancer cells, Transient constitutive expression of a dominant negative c -jun mutant (TAM67) in human AZ224, SKOV3 and OVCAR3 ovarian cancer cells i nhibited the outgrowth of selection marker-resistant colonies by at least 7 5% as opposed to a control plasmid, Transfection of jun-B did not affect th ese cell lines, while jun-D transfection had a cell line-specific effect. I n comparison, transfection of the tumor-suppressor gene p53 had a less impo rtant inhibitory effect on OVCAR3 cells and no effect on SKOV3 and AZ224 ce lls when compared to TAM67, Regulated TAM67 expression in AZ224 cells, from plasmids containing the mouse metallothionein or the MMTV promoter, suppre ssed cancer cell growth in vitro and in nude mice without evidence of incre ased cell death. Our observations support a role for the c-jun proto-oncoge ne as a positive mediator of human ovarian cancer cell growth and make it a potential therapeutic target. Int. J. Cancer 82:687-693, 1999, (C) 1999 Wi ley-Liss, Inc.