Regulation of UT-OC-3 ovarian carcinoma cells by cytokines: inhibitory effects on cell proliferation and activation of transcription factors AP-1 andNF-kappa B

Citation
M. Seppanen et al., Regulation of UT-OC-3 ovarian carcinoma cells by cytokines: inhibitory effects on cell proliferation and activation of transcription factors AP-1 andNF-kappa B, EUR J ENDOC, 142(4), 2000, pp. 393-401
Citations number
49
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
EUROPEAN JOURNAL OF ENDOCRINOLOGY
ISSN journal
08044643 → ACNP
Volume
142
Issue
4
Year of publication
2000
Pages
393 - 401
Database
ISI
SICI code
0804-4643(200004)142:4<393:ROUOCC>2.0.ZU;2-5
Abstract
The present study was designed to investigate the growth regulatory effects of cytokines in UT-OC-3 ovarian cystadenocarcinoma cells in vitro. The eff ects of interleukin-6 (IL-6), interferons alpha (IFN-alpha) and gamma (IFN- gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour n ecrosis factor alpha (TNF-alpha), and transforming growth factor beta 1 (TG F-beta 1) were investigated by I-125-deoxyuridine ((125)IUdR) incorporation assay. In order to understand better the molecular mechanisms of the obser ved effects, the activation of DNA-binding proteins was studied by electrop horetic mobility shift assay. In addition, cellular DNA was tested by fragm entation analysis to determine if the most growth inhibitory cytokines are able to induce programmed cell death (apoptosis). After 48 h in culture, TG F-beta 1, TNF-alpha, IFN-alpha and IL-6 showed a clear inhibitory effect on (125)IUdR incorporation (P < 0.005), and IFN-gamma and GM-CSF caused even more significant inhibition (P < 0.001). IFN-alpha and IFN-gamma were both growth inhibitory after 72 h in culture (P < 0.005). Similarly, GM-CSF indu ced a slight inhibition (P < 0.05); whereas TGF-beta 1 and TNF-alpha almost blocked DNA synthesis (P < 0.001) after 72 h. IL-6 had no statistically si gnificant effect on cell proliferation after 72 h. Transcription factors AP -1 and NF-kappa B were both constitutively expressed in UT-OC-3 cells. The binding activity of AP-1 was found to be stimulated by the growth inhibitor y cytokines, TGF-beta 1 and TNF-alpha, and the binding of NF-kappa B was st imulated by TNF-alpha. Apoptosis does not seem to be induced by any of thes e cytokines in the UT-OC-S ovarian cancer cell model.