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Conference Paper: The role of estrogen receptor subtypes in ovarian hormonal therapy

TitleThe role of estrogen receptor subtypes in ovarian hormonal therapy
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research.
Citation
The 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA., 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. 3272 How to Cite?
AbstractEstrogen, a steroid hormone mainly synthesized in the ovary, regulates the expression of genes that are responsible for cell proliferation, apoptosis, tumor metastasis and invasion. The effects of estrogen are mediated through estrogen receptors (ER). Previous investigations demonstrated that two major subtypes of ER (α and β) had opposing effects on cell proliferation: ERα promoted cell proliferation, whereas ERβ induced cell apoptosis. Although ovarian cells bear hormone receptors and are hormone sensitive, hormonal therapy in ovarian cancer is not well established. The relationship between cellular responses to hormonal therapy and the expressions of estrogen receptor subtypes is still unclear. The aim of this study was to investigate the cellular responses of ovarian cancer to selective estrogen receptor modulators in relation to estrogen receptor subtypes expressions. In this study, the effects of a spectrum of estrogen receptor agonist, partial agonist and a newly discovered pure antagonist on the growth of ovarian cancer cells bearing different estrogen receptor subtypes were studied. Using Real-time PCR, we found that 41.6% of ovarian cancer cell lines (5 of 12) showed higher ERα than ERβ mRNA levels (ERα/ERβ ratio>1) whereas all seven normal ovarian cell lines showed higher ERβ levels. Four ovarian cancer cell lines with different expression profiles (ERα+/ERβ+, ERα-/ERβ-, ERα-/ERβ+, ERα+/ERβ-) were selected. Apoptosis and clonogenic assays were used to detect the effects of drugs on cell apoptosis and proliferation respectively. Estradiol (agonist) significantly reduced apoptosis and increased survival of α+/β+ and α+/β- cells, but it had no effect on α-/β- or α-/β+ cells, implying that Estradiol promoted the growth of ovarian cancer cells bearing the ERα receptor subtype. Fulvestrant (pure antagonist) increased apoptosis and reduced survival in all four different cell lines, suggesting that its effects were mediated via a receptor-independent pathway. Tamoxifen (partial agonist) induced apoptosis of α+/β- and α-/β+ cells at different concentrations, but had no effect on α+/β+ and α-/β-cells, suggesting Tamoxifen might have a partial agonist effect on ERα positive cells but a pure antagonist effect on ERβ positive cells. These findings provided some insights into the use of hormonal therapy in ovarian cancer patients with different estrogen receptor subtypes expression profiles.
Persistent Identifierhttp://hdl.handle.net/10722/113762
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorWei, Nen_HK
dc.contributor.authorChan, KKLen_HK
dc.contributor.authorLiu, Sen_HK
dc.contributor.authorChan, YKen_HK
dc.contributor.authorLeung, CYen_HK
dc.contributor.authorNgan, HYSen_HK
dc.date.accessioned2010-09-26T04:30:05Z-
dc.date.available2010-09-26T04:30:05Z-
dc.date.issued2007en_HK
dc.identifier.citationThe 98th Annual Meeting of the American Association for Cancer Research (AACR 2007), Los Angeles, CA., 14-18 April 2007. In Cancer Research, 2007, v. 67 n. 9S, p. 3272-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/113762-
dc.description.abstractEstrogen, a steroid hormone mainly synthesized in the ovary, regulates the expression of genes that are responsible for cell proliferation, apoptosis, tumor metastasis and invasion. The effects of estrogen are mediated through estrogen receptors (ER). Previous investigations demonstrated that two major subtypes of ER (α and β) had opposing effects on cell proliferation: ERα promoted cell proliferation, whereas ERβ induced cell apoptosis. Although ovarian cells bear hormone receptors and are hormone sensitive, hormonal therapy in ovarian cancer is not well established. The relationship between cellular responses to hormonal therapy and the expressions of estrogen receptor subtypes is still unclear. The aim of this study was to investigate the cellular responses of ovarian cancer to selective estrogen receptor modulators in relation to estrogen receptor subtypes expressions. In this study, the effects of a spectrum of estrogen receptor agonist, partial agonist and a newly discovered pure antagonist on the growth of ovarian cancer cells bearing different estrogen receptor subtypes were studied. Using Real-time PCR, we found that 41.6% of ovarian cancer cell lines (5 of 12) showed higher ERα than ERβ mRNA levels (ERα/ERβ ratio>1) whereas all seven normal ovarian cell lines showed higher ERβ levels. Four ovarian cancer cell lines with different expression profiles (ERα+/ERβ+, ERα-/ERβ-, ERα-/ERβ+, ERα+/ERβ-) were selected. Apoptosis and clonogenic assays were used to detect the effects of drugs on cell apoptosis and proliferation respectively. Estradiol (agonist) significantly reduced apoptosis and increased survival of α+/β+ and α+/β- cells, but it had no effect on α-/β- or α-/β+ cells, implying that Estradiol promoted the growth of ovarian cancer cells bearing the ERα receptor subtype. Fulvestrant (pure antagonist) increased apoptosis and reduced survival in all four different cell lines, suggesting that its effects were mediated via a receptor-independent pathway. Tamoxifen (partial agonist) induced apoptosis of α+/β- and α-/β+ cells at different concentrations, but had no effect on α+/β+ and α-/β-cells, suggesting Tamoxifen might have a partial agonist effect on ERα positive cells but a pure antagonist effect on ERβ positive cells. These findings provided some insights into the use of hormonal therapy in ovarian cancer patients with different estrogen receptor subtypes expression profiles.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Researchen_HK
dc.titleThe role of estrogen receptor subtypes in ovarian hormonal therapyen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, KKL: karenchan@pobox.comen_HK
dc.identifier.emailLiu, S: stephasl@HKUCC.hku.hken_HK
dc.identifier.emailChan, YK: kelvinc@pathology.hku.hken_HK
dc.identifier.emailLeung, CY: cyleungr@HKUCC.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.authorityChan, KKL=rp00499en_HK
dc.identifier.authorityLiu, S=rp00372en_HK
dc.identifier.authorityChan, YK=rp00453en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.hkuros141196en_HK
dc.identifier.volume67-
dc.identifier.issue9S-
dc.identifier.spage3272-
dc.identifier.epage3272-

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