Estrogen Receptor Subtypes in Ovarian Cancer

Ky, Chan; Wei, Na; Liu, Stephanie S.; Xiao-Yun, Liao; Cheung, Annie N.Y.; Ngan, Hextan Y.S.

doi:10.1097/01.aog.0000296715.07705.e9

Cited by 100 publications

(85 citation statements)

References 13 publications

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“…As hormone-sensitive cancer, a large subset of ovarian cancers is associated with the deregulation of ERα or AR (Rao et al, 1991;Chan et al, 2008). Our study demonstrated that ATAD2 is overexpressed in ovarian cancers.…”

Section: Discussionmentioning

confidence: 54%

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

Wan¹,

Zhang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The purpose of this study was to explore the expression of ATAD2 in ovarian tumor tissue as well as its relationship with degree of malignancy. Tumor tissue from 110 cases of ovarian cancer was collected in accordance with the Declaration of Helsinki for evaluation of ATAD2 expression iimmunohistochemistry, quantitative PCR (qPCR) and Western blotting. The correlation between the ATAD2 expression and and the prognosis of ovarian cancer was evaluated by Cox regression model. In addition, HO-8910 and OVCAR-3 cells were transfected with two siRNAs targeting ATAD2. Cell viability was evaluated with MTT assay, and cell migration by transwell migration assay. ATAD2 was shown to be highly expressed in 65.5% (72/110) of ovarian cancer cases, both at transcriptional and protein levels. Moreover, highly expression was positively correlated with degree of malignancy. Knock-down of ATAD2 in HO-8910 and OVCAR-3 cells was found to reduce cell migration. In addition, follow-up visits of the patients demonstrated that the 5-year survival rate was lower in patients with high expression of ATAD2. Our study suggested that ovarian tumor tissue may have highly expressed ATAD2, which is associated with tumor stage, omentum-metastasis, ascites and CA-125. Increased ATAD2 may play important roles in tumor proliferation and migration. ATAD2 could serve in particular as a prognostic marker and a therapeutic target for ovarian cancer.

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Section: Discussionmentioning

confidence: 54%

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

Wan¹,

Zhang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Two groups have investigated ER expression on the RNA level using fresh frozen ovarian tumor tissue. Chan et al (2008) found a prognostic impact of ESR2 but not ESR1 mRNA expression; however, the significance of these results is limited by the fact that epithelial and non-epithelial malignant ovarian tumors as well as borderline tumors were evaluated together. Fujimoto et al (2000) found the ratio ESR2 to ESR1 mRNA to be prognostic for ovarian cancer patients but did not evaluate ER mRNA expression quantitatively and used a very small sample size (28 patients) for the analysis.…”

Section: Discussionmentioning

confidence: 78%

Estrogen receptor 1 mRNA is a prognostic factor in ovarian carcinoma: determination by kinetic PCR in formalin-fixed paraffin-embedded tissue

Darb‐Esfahani

Wirtz

Sinn³

et al. 2009

Endocrine-Related Cancer

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Epidemiological and cell culture studies indicate that ovarian carcinoma growth is dependent on estrogen stimulation. However, possibly due to the lack of a reliable biomarker that helps to select patients according to prognostically relevant estrogen receptor (ER) levels, clinical trials using anti-estrogenic therapeutics in ovarian carcinoma have had inconsistent results. Therefore, we tested if ER expression analysis by a quantitative method might be useful in this regard in formalinfixed paraffin-embedded (FFPE) tissue. In a study group of 114 primary ovarian carcinomas expression of estrogen receptor 1 (ESR1) mRNA was analyzed using a new method for RNA extraction from FFPE tissue that is based on magnetic beads, followed by kinetic PCR. The prognostic impact of ESR1 mRNA expression was investigated and compared to ERa protein expression as determined by immunohistochemistry. In univariate survival analysis the expression level of ESR1 mRNA was a significant positive prognostic factor for patient survival (hazard ratio (HR) 0.230 (confidence interval (CI) 0.102-0.516), PZ0.002). ERa protein expression was correlated to ESR1 mRNA expression (PZ0.0001); however, ERa protein expression did not provide statistically significant prognostic information. In multivariate analysis, ESR1 mRNA expression emerged as a prognostic factor, independent of stage, grade, residual tumor mass, age, and ERa protein expression (HR 0.227 (CI 0.078-0.656), PZ0.006). Our results indicate that the determination of ESR1 levels by kinetic PCR may be superior to immunohistochemical methods in assessment of biologically relevant levels of ER expression in ovarian carcinoma, and is feasible in routinely used FFPE tissue.

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“…These initial findings had not taken into account the presence of ER subtypes. Both ERa and ERb were found to be present in both normal ovarian tissues and ovarian cancer tissues, with a possible reduction of ERb expression as tumors progress (Bardin et al 2004a, Chan et al 2008. The loss of ERb expression indicates that ERb exerts tumor-suppressive functions and may have a protective role.…”

Section: Discussionmentioning

confidence: 99%

“…Since then, ERb has been found in most estrogen-target tissues such as the prostate (Weihua et al 2001) and the ovary (Brandenberger et al 1998). Reduced levels of ERb mRNA expression were found in malignant tissues compared with normal tissues in various estrogendependent tumors such as breast, prostate, and ovarian cancers (Iwao et al 2000, Horvath et al 2001, Skliris et al 2003, Chan et al 2008, indicating that the loss of ERb expression may be involved in carcinogenesis. This is further supported by the findings that ectopic expression of ERb in breast, prostate, and ovarian cancer cells inhibits motility and cell invasion and leads to increased apoptosis (Lazennec et al 2001, Cheng et al 2004.…”

Section: Introductionmentioning

confidence: 99%

Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer

Chan

Leung

Chan

et al. 2014

Journal of Endocrinology

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Ovarian cancer cells express both estrogen receptor a (ERa) and ERb, and hormonal therapy is an attractive treatment option because of its relatively few side effects. However, estrogen was previously shown to have opposite effects in tumors expressing ERa compared with ERb, indicating that the two receptor subtypes may have opposing effects. This may explain the modest response to nonselective estrogen inhibition in clinical practice. In this study, we aimed to investigate the effect of selectively targeting each ER subtype on ovarian cancer growth. Ovarian cancer cell lines SKOV3 and OV2008, expressing both ER subtypes, were treated with highly selective ER modulators. These results were confirmed on a xenograft model where SKOV3 cells were injected s.c. into ovariectomized mice. We observed that the average size of xenografts in both the DPN-treated group and the MPP-treated group was significantly smaller than that for the vehicle-treated group. In addition, we found that phospho-AKT expressions in SKOV3 cells were reduced by 80% after treatment with MPP and DPN, indicating that the AKT pathway was involved. The combined treatment with MPP and DPN had a synergistic effect in suppressing ovarian cancer cell growth. Our findings indicate that targeting ER subtypes may enhance the response to hormonal treatment in women with ovarian cancer.

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Estrogen Receptor Subtypes in Ovarian Cancer

Abstract: II.

Cited by 100 publications

References 13 publications

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

Estrogen receptor 1 mRNA is a prognostic factor in ovarian carcinoma: determination by kinetic PCR in formalin-fixed paraffin-embedded tissue

Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer

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