We have successfully established an ovarian cancer cell line (OVTW-59), which was derived from an ovarian endometrioid carcinoma (EC), and have also established an ovarian EC invasion model. By using cDNA microarray and quantitative reverse-transcriptase polymerase chain reaction, we identified insulin-like growth factor binding protein (IGFBP)-3 as an invasion suppressor gene, which were associated with lower cancer migration, invasion and metastasis. Clinically, lower IGFBP-3 was found associated with significantly higher tumor grade, advanced stage and poor survival in patients with EC tumors. Furthermore, we have proved IGFBP-3 expression correlated with lower Erk activation, but with no effect on the activation of Akt. All these two signal transduction proteins have crucial roles in cancer invasion. Recently, a novel model of ovarian EC formation from endometriosis was reported, and PTEN was found to be a major protein involved. Inactivation of PTEN has been reported in some ovarian EC tumors and methylation was suggested as one of the major epigenetic changes. This tumorigenesis model has lots of similarity to our established invasion model. Therefore, we plan to study the important of PTEN expression in ovarian EC and if inactivation of PTEN and IFGBP-3 is through methylation. Furthermore, by studying the signal transduction pathways using PTEN and IGFBP-3 transfection, we plan to study the mutual interaction between PTEN and IGFBP-3 on the suppression of tumor invasion in ovarian EC.
