Characterization of immortalized human ovarian surface epithelial cells transfected by PTEN expression vectors

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Epithelial ovarian carcinomas are thought to arise from cells of ovarian surface epithelium (OSE) covering the free surface of the human ovary. Two immortalized human cell lines, OSE2a (non-tumorigenic) and OSE2b-2 (tumorigenic), were previously established from normal OSE cells of a reproductive-age patient. In the present project, we found that expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (R) is present in OSE2a cells and absent in OSE2b-2 cells. In OSE2a cells, a low concentration (10^3 mIU/ml) of hCG enhanced anchorage-dependent growth via up-regulation of insulin-like growth factor-1 (IGF1), whereas a high concentration (10^5 mlU/ml) of hCG induced anchorage-independent growth and down-regulation of IGF1 expression. To investigate involvement of other genes in LH/hCGR-related tumorigenicity, we compared cDNA expression arrays between OSE2a and OSE2b-2 cells, and found that the following genes had lower expression in OSE2b-2 than in OSE2a: integrin β1, intercellular adhesion molecule-1 (ICAM1), and Wafl/Cipl. Subsequent semiquantitative reverse transcription porymerase chain reaction using OSE2a cells showed that expression of integrin β1 was down-regulated by a high concentration (10^5 mlU/ml) of hCG. These results suggest that LH/CGR affects anchorage-dependent and -independent growth by mediating up- and down-regulation of IGF1 and integrin β1. Repetitive and excessive activation of LH/hCGR may cause genetic alteration of its signal transduction pathway, resulting in stimulation of growth of OSE cells, initiation of ovarian carcinogenesis, and cancer progression. We have submitted a manuscript for this study to 'Cancer Science'.Regarding the PTEN gene, the functional analysis of LH/hCGR preceded the study for characterization of immortalized OSE cells trasfected by PTEN expression vectors. We still farther study the project for the PTEN expression.