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Tissue inhibitors of metalloproteinases (TIMPs) play a key role in maintaining homeostasis of the extracellular matrix (ECM) by controlling matrix metalloproteinases (MMPs). In addition to their role in regulating MMPs, TIMPs have been shown to also have pluripotential effects on cell growth, apoptosis and differentiation. The aim of this study was to examine TIMP-2 level in serous ovarian tumor tissues and to further understand the role of TIMP-2 protein in ovarian tumorigenesis. In a total of 57 ovarian specimens including 5 normal ovaries, 12 benign serous cystadenomas, 20 serous borderline tumors and 20 serous carcinomas, expression of TIMP-2 was assessed by immunohistochemical staining. In order to understand the effect of TIMP-2 overexpression in cell lines, we performed an apoptosis assay as well as a MTT assay by transfecting TIMP-2 vector into SKOV3, 2774 and HeLa cell lines. The study results demonstrated that immunohistochemical staining of TIMP-2 was observed to be significantly more frequent in serous carcinomas when compared to the other groups. A transient overexpression of TIMP-2 caused dramatic reduction of cell growth and a change in cell morphology only in HeLa cells, not in 2774 or SKOV3 cells. These results demonstrate that TIMP-2 is up-regulated in serous ovarian carcinoma tissues when compared to normal ovarian tissues; it dose not mediate pro-apoptotic activity in ovarian cancer cell lines, however, it does mediate pro-apoptotic activity in cervical cancer cells. These findings suggest that TIMP-2 may function in favor of tumor growth in serous ovarian tumorigenesis. Additional research is now needed to further elucidate the role of TIMP-2 in the biological behavior of ovarian serous carcinoma.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]