title: Roles of luteinizing hormone/chorionic gonadotropin receptor in anchorage-dependent and -independent growth in human ovarian surface epithelial cell lines.
abstract: 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 study, we found that expression of luteinizing hormone (LH)/chorionic gonadotropin (CG) receptor (LH/CGR) is present in OSE2a cells and absent in OSE2b-2 cells. In OSE2a cells, a low concentration (10(3) mIU/ml) of CG enhanced anchorage-dependent growth via up-regulation of insulin-like growth factor-1 (IGF1), whereas a high concentration (10(5) mIU/ml) of CG induced anchorage-independent growth and down-regulation of IGF1 expression. To investigate involvement of other genes in LH/CGR-related tumorigenicity, we compared cDNA expression arrays of OSE2a and OSE2b-2 cells, and found that the following genes had lower expression in OSE2b-2 than in OSE2a: integrin beta 1, intercellular adhesion molecule-1 (ICAM1), and Waf1/Cip1. Subsequent semiquantitative reverse transcription polymerase chain reaction using OSE2a cells showed that expression of integrin beta 1 was down-regulated by a high concentration (10(5) mIU/ml) of CG. These results suggest that LH/CGR affects anchorage-dependent and -independent growth by mediating up- and down-regulation of IGF1 and integrin beta 1. Repetitive and excessive activation of LH/CGR may cause genetic alteration of its signal transduction pathway, resulting in stimulation of growth of OSE cells, initiation of ovarian carcinogenesis, and cancer progression.
authors: Department of Obstetrics and Gynecology, Kumamoto University School of Medicine, Kumumoto City, Kumamoto 860-8556.
authors: Hironori
authors: H
authors: Tashiro
authors: Hidetaka
authors: H
authors: Katabuchi
authors: Monjura
authors: M
authors: Begum
authors: Xiaoguang
authors: X
authors: Li
authors: Makoto
authors: M
authors: Nitta
authors: Hideyuki
authors: H
authors: Ohtake
authors: Hitoshi
authors: H
authors: Okamura
mesh_terms: D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010053:Ovary / Q000187:drug effects*; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: C493956:CDKN1A protein, human; D006063:Chorionic Gonadotropin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019012:Integrin beta1; D011974:Receptors, LH; D018799:Intercellular Adhesion Molecule-1; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone