title: Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation.
abstract: BACKGROUND
  Since a substantial percentage of ovarian cancers express gonadotropin receptors and are responsive to the relatively high concentrations of pituitary gonadotropins during the postmenopausal years, it has been suggested that receptor activation may contribute to the etiology and/or progression of the neoplasm. The goal of the present study was to develop a cell model to determine the impact of luteinizing hormone (LH) receptor (LHR) expression and LH-mediated LHR activation on gene expression and thus obtain insights into the mechanism of gonadotropin action on ovarian surface epithelial (OSE) carcinoma cells.
  
  
  METHODS
  The human ovarian cancer cell line, SKOV-3, was stably transfected to express functional LHR and incubated with LH for various periods of time (0-20 hours). Transcriptomic profiling was performed on these cells to identify LHR expression/activation-dependent changes in gene expression levels and pathways by microarray and qRT-PCR analyses.
  
  
  RESULTS
  Through comparative analysis on the LHR-transfected SKOV-3 cells exposed to LH, we observed the differential expression of 1,783 genes in response to LH treatment, among which five significant families were enriched, including those of growth factors, translation regulators, transporters, G-protein coupled receptors, and ligand-dependent nuclear receptors. The most highly induced early and intermediate responses were found to occupy a network impacting transcriptional regulation, cell growth, apoptosis, and multiple signaling transductions, giving indications of LH-induced apoptosis and cell growth inhibition through the significant changes in, for example, tumor necrosis factor, Jun and many others, supportive of the observed cell growth reduction in in vitro assays. However, other observations, e.g. the substantial up-regulation of the genes encoding the endothelin-1 subtype A receptor, stromal cell-derived factor 1, and insulin-like growth factor II, all of which are potential therapeutic targets, may reflect a positive mediation of ovarian cancer growth.
  
  
  CONCLUSIONS
  Overall, the present study elucidates the extensive transcriptomic changes of ovarian cancer cells in response to LH receptor activation, which provides a comprehensive and objective assessment for determining new cancer therapies and potential serum markers, of which over 100 are suggested.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Cui
authors.forename: Brooke M
authors.initials: BM
authors.lastname: Miner
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Eldredge
authors.forename: Susanne W
authors.initials: SW
authors.lastname: Warrenfeltz
authors.forename: Phuongan
authors.initials: P
authors.lastname: Dam
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: David
authors.initials: D
authors.lastname: Puett
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007986:Luteinizing Hormone / Q000494:pharmacology / Q000502:physiology*; D009363:Neoplasm Proteins / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D011974:Receptors, LH / Q000819:agonists / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH; D011993:Recombinant Fusion Proteins; D007986:Luteinizing Hormone