Alteration of Jun proto-oncogene status by plasmid transfection affects growth of human ovarian cancer cells
Bart Neyns
Laboratory of Molecular Oncology and Oncology Center, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorEric Teugels
Laboratory of Molecular Oncology and Oncology Center, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorClaire Bourgain
Laboratory of Experimental Pathology, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorMichael Birrerand
National Cancer Institute, Division of Cancer Prevention and Control, Biomarkers and Prevention Research Branch, Rockville, MD, USA
Search for more papers by this authorCorresponding Author
Jacques De Grève
Laboratory of Molecular Oncology and Oncology Center, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Medical Oncology, Akademisch Ziekenhuis, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Fax: +32 2 477 62 10.Search for more papers by this authorBart Neyns
Laboratory of Molecular Oncology and Oncology Center, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorEric Teugels
Laboratory of Molecular Oncology and Oncology Center, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorClaire Bourgain
Laboratory of Experimental Pathology, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Search for more papers by this authorMichael Birrerand
National Cancer Institute, Division of Cancer Prevention and Control, Biomarkers and Prevention Research Branch, Rockville, MD, USA
Search for more papers by this authorCorresponding Author
Jacques De Grève
Laboratory of Molecular Oncology and Oncology Center, Akademisch Ziekenhuis Vrije Universiteit Brussel, Brussels, Belgium
Medical Oncology, Akademisch Ziekenhuis, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. Fax: +32 2 477 62 10.Search for more papers by this authorAbstract
The AP-1 transcription factor (the Jun and Fos proteins) is suspected of playing an important role in the biology of human cancer. Human epithelial ovarian tumors and cancer cell lines express the c-jun and jun-B proto-oncogenes 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 ovarian cancer cells. Transient constitutive expression of a dominant negative c-jun mutant (TAM67) in human AZ224, SKOV3 and OVCAR3 ovarian cancer cells inhibited the outgrowth of selection marker–resistant colonies by at least 75% as opposed to a control plasmid. Transfection of jun-B did not affect these cell lines, while jun-D transfection had a cell line–specific effect. In comparison, transfection of the tumor-suppressor gene p53 had a less important inhibitory effect on OVCAR3 cells and no effect on SKOV3 and AZ224 cells when compared to TAM67. Regulated TAM67 expression in AZ224 cells, from plasmids containing the mouse metallothionein or the MMTV promoter, suppressed cancer cell growth in vitro and in nude mice without evidence of increased cell death. Our observations support a role for the c-jun proto-oncogene as a positive mediator of human ovarian cancer cell growth and make it a potential therapeutic target. Int. J. Cancer 82:687–693, 1999. © 1999 Wiley-Liss, Inc.
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