Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation

Juan Cui, Brooke M. Miner, Joanna B. Eldredge, Susanne W. Warrenfeltz, Phuongan Dam, Ying Xu, David Puett

Research output: Contribution to journalArticle

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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.Conclusion: 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.

Original languageEnglish (US)
Article number280
JournalBMC cancer
Volume11
DOIs
StatePublished - Jun 28 2011

Fingerprint

LH Receptors
Gene Expression Regulation
Ovarian Neoplasms
Luteinizing Hormone
Growth
Gonadotropin Receptors
Apoptosis
Pituitary Gonadotropins
Gene Expression
Chemokine CXCL12
Insulin-Like Growth Factor II
Gene Regulatory Networks
Endothelin-1
Cytoplasmic and Nuclear Receptors
G-Protein-Coupled Receptors
Gonadotropins
Genes
Neoplasms
Intercellular Signaling Peptides and Proteins
Up-Regulation

Keywords

  • Gonadotropin
  • Luteinizing hormone
  • Luteinizing hormone receptor
  • Microarray
  • Ovarian cancer
  • SKOV3 cells

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this

Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation. / Cui, Juan; Miner, Brooke M.; Eldredge, Joanna B.; Warrenfeltz, Susanne W.; Dam, Phuongan; Xu, Ying; Puett, David.

In: BMC cancer, Vol. 11, 280, 28.06.2011.

Research output: Contribution to journalArticle

Cui, Juan ; Miner, Brooke M. ; Eldredge, Joanna B. ; Warrenfeltz, Susanne W. ; Dam, Phuongan ; Xu, Ying ; Puett, David. / Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation. In: BMC cancer. 2011 ; Vol. 11.
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AU - Cui, Juan

AU - Miner, Brooke M.

AU - Eldredge, Joanna B.

AU - Warrenfeltz, Susanne W.

AU - Dam, Phuongan

AU - Xu, Ying

AU - Puett, David

PY - 2011/6/28

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N2 - 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.Conclusion: 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.

AB - 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.Conclusion: 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.

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KW - Luteinizing hormone

KW - Luteinizing hormone receptor

KW - Microarray

KW - Ovarian cancer

KW - SKOV3 cells

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