Roles of luteinizing hormone/chorionic gonadotropin receptor in anchorage-dependent and -independent growth in human ovarian surface epithelial cell lines

Cancer Sci. 2003 Nov;94(11):953-9. doi: 10.1111/j.1349-7006.2003.tb01384.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion*
  • Cell Division
  • Cells, Cultured / drug effects
  • Chorionic Gonadotropin / pharmacology*
  • Colony-Forming Units Assay
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Cyclins / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Luteinizing Hormone / pharmacology*
  • Oligonucleotide Array Sequence Analysis
  • Ovary / drug effects*
  • Receptors, LH / genetics
  • Receptors, LH / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction


  • CDKN1A protein, human
  • Chorionic Gonadotropin
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Integrin beta1
  • Receptors, LH
  • Intercellular Adhesion Molecule-1
  • Insulin-Like Growth Factor I
  • Luteinizing Hormone