Ovarian Carcinoma Cell Cultures Are Resistant to TGF-β1-Mediated Growth Inhibition Despite Expression of Functional Receptors

• Published in: Gynecologic oncology Vol. 75; no. 1; pp. 72 - 77
• Main Authors: Yamada, S.Diane, Baldwin, Rae Lynn, Karlan, Beth Y.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: San Diego, CA Elsevier Inc 01.10.1999; Elsevier
• Subjects: Biological and medical sciences; Female genital diseases; growth; Gynecology. Andrology. Obstetrics; matrix metalloproteinase; Medical sciences; ovarian cancer; transforming growth factor-β; transforming growth factor-β receptor; Tumors; matrix metalloproteinase; growth; transforming growth factor-β receptor; transforming growth factor-β; ovarian cancer; Human; Carcinoma; Enzyme; Transforming growth factor; Cytokine; Metalloendopeptidases; Malignant tumor; Carcinogenesis; Female genital diseases; Gelatinase A; Resistance; Ovarian diseases; Peptidases; Ovary; Growth factor receptor; Polypeptide; Hydrolases; Female; Transforming growth factor β1; Growth factor
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.1999.5535

Objective. The purpose of this study was to determine the response of ovarian carcinoma cells to TGF-β1 and to examine components of the TGF-β signaling pathway. Methods. Twenty-three primary ovarian cancer cell (CSOC) cultures established from solid ovarian carcinomas were treated with TGF-β1 and assayed for growth response by MTT assay. Expression of TGF-β receptor I (TβR-I) and receptor II (TβR-II), essential for effective signaling, was determined by Western analysis of CSOC cultures. TGF-β1 ligand-induced phosphorylation of TβR-I was determined by immunoprecipitation of TβR-I followed by a protein kinase assay to assess TβR-I phosphorylation, an essential first step in TGF-β signal transduction. Gelatin zymography performed on 5 CSOC cultures incubated with TGF-β1 was used to determine TGF-β's effect on matrix metalloproteinase production. Normal ovarian surface epithelial cells were used for comparison. Results. Eighteen of twenty-three (78%) CSOC cultures demonstrated no significant growth inhibition in response to TGF-β1 treatment. All cell cultures expressed TβR-I and TβR-II and exhibited TβR-I phosphorylation following TGF-β1 treatment. CSOC cultures produced significantly higher levels of matrix metalloproteinase-2 (MMP-2) than normal ovarian surface epithelial cells; however, the level of MMP-2 expression was not regulated by TGF-β1. Conclusion. These results indicate that TGF-β1 resistance and higher levels of MMP-2 production may be inherent properties of the ovarian cancer phenotype. The initial steps in the TGF-β signaling pathway, receptor expression, ligand binding, and TβR-I phosphorylation, appear to be functional in primary ovarian cancer cell cultures. Therefore, the mechanism of growth resistance is downstream of TβR-I phosphorylation.