Is oestrogen receptor- β a predictor of endocrine therapy responsiveness in human breast cancer?

Murphy, Leigh C.; Watson, Peter H.

doi:10.1677/erc.1.01141

Cited by 69 publications

(64 citation statements)

References 47 publications

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“…Moreover, loss of ERb was observed to be associated with tamoxifen resistance whereas increase of ERb expression in MCF-7 cells enhanced the antiproliferative and apoptotic effect of antiestrogens (HodgesGallagher et al, 2008). However, data regarding the association of ERb expression with clinical pathological parameters and antiestrogen responsiveness are still mixed (Speirs et al, 1999;O'Neill et al, 2004;Murphy and Watson, 2006).…”

Section: Discussionmentioning

confidence: 99%

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

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We have previously identified an oncogenic role of artemin (ARTN), a member of glial cell derived neurotrophic factor family of ligands, in mammary carcinoma. We herein report that ARTN is an estrogen-inducible gene. Metaanalysis of gene expression data sets showed that ARTN expression is positively correlated to estrogen receptor (ER) status in human mammary carcinoma. Furthermore, in patients with ER-positive mammary carcinoma treated with tamoxifen, high ARTN expression is significantly correlated with decreased survival. Forced expression of ARTN in ER-positive human mammary carcinoma cells increased ER transcriptional activity, promoted estrogenindependent growth and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. ARTN-stimulated resistance to tamoxifen and fulvestrant is mediated by increased BCL-2 expression. Conversely, depletion of endogenous ARTN by smallinterfering RNA or functional antagonism of ARTN by antibody enhanced the efficacy of antiestrogens. Tamoxifen decreased ARTN expression in tamoxifen-sensitive mammary carcinoma cells whereas ARTN expression was increased in tamoxifen-resistant cells and not affected by tamoxifen treatment. Antibody inhibition of ARTN in tamoxifen-resistant cells improved tamoxifen sensitivity. Functional antagonism of ARTN therefore warrants consideration as an adjuvant therapy to enhance antiestrogen efficacy in ER-positive mammary carcinoma.

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Section: Discussionmentioning

confidence: 99%

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

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“…RT-PCR fails to take into account translational control or turnover of protein, and has the potential to measure ER expression in contaminating cell types such as normal epithelial and stromal vascular cells [78,79]. The region of the mRNA targeted by primers may also influence which variants are detected.…”

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

“…Recently, reliable antibodies detecting either N-(such as Ab288/14C8) or C-terminal (such as GC17/385P) epitopes of ERβ have been developed [79]. N-terminal antibodies recognize both full-length ERβ and its splice variants (Fig.…”

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

“…N-terminal antibodies recognize both full-length ERβ and its splice variants (Fig. 1), whereas ERβ C-terminal antibodies specifically detect the wild type or variant forms of ERβ [79] and allow distinctions to be made between full-length ERβ and its variants. Both antibody types have been used; however, sample preparation and integrity as well as specific staining protocols may influence outcomes [79].…”

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

“…1), whereas ERβ C-terminal antibodies specifically detect the wild type or variant forms of ERβ [79] and allow distinctions to be made between full-length ERβ and its variants. Both antibody types have been used; however, sample preparation and integrity as well as specific staining protocols may influence outcomes [79]. With variation in the choice of ERβ antibody and tissue fixation protocols, there is not yet firm agreement on the appropriate cutoff value for determining ERβ positivity [78,82].…”

Section: Coexpression Of Erβ With Erα and Other Potential Markers In mentioning

confidence: 99%

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ERβ in breast cancer—Onlooker, passive player, or active protector?

2008

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The role of estrogen exposure in breast cancer risk is well-documented, and both estrogen synthesis and actions through the estrogen receptor (ER) have been targeted by therapies to control hormonedependent breast cancer. The discovery of a second ER form and its therapeutic implications sparked great interest. Both the original ERα and the more recently identified ERβ subtypes bind and respond similarly to many physiological and pharmacological ligands. However, differences in phytoestrogen binding have been noted, and subtype-specific ligands have been developed. Cell-based assays show that ERβ and its variants are generally less active on gene transcription than ERα, and may influence ERα activity; however, both gene-and cell-specific responses occur, and nongenomic activities are less well explored. Specific ligands, and methods to disrupt or eliminate receptor subtype expression in animal and cell models, demonstrate that the ERs have both overlapping and distinct biological functions. Overall, in cell-based studies, ERα appears to play a predominant role in cell proliferation, and ERβ is suggested to be antiproliferative.The potential for distinct populations of breast tumors to be identified based on ER subtype expression, and to exhibit distinct clinical behaviors, is of greatest interest. Several studies suggest that the majority of ER-positive tumors contain both subtypes, but that some tumors contain only ERβ and may have distinct clinical behaviors and responses. Expression of ERβ together with ERα favors positive responses to endocrine therapy in most studies, and additional studies to determine if the addition of ERβ to ERα as a tumor marker is of clinical benefit are warranted. In contrast, the positive association between ERβ and HER2 expression in high-grade ERα-negative breast cancer does not favor positive responses to endocrine therapy. Expression of ERβ in specific clinical subpopulations, and the potential for therapies targeting ERβ specifically, is discussed.

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Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice

Giroux

Lemay

Bernatchez

et al. 2008

Intl Journal of Cancer

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Clinical evidence suggests that estradiol replacement therapy reduces colon cancer risk in ‘post’menopausal women. In colon epithelial cells, the estrogen receptor β (ERβ) is the predominant ER subtype and is thought to mediate the genomic effect of estrogens. The first aim of this study was to investigate the consequence of ERβ deficiency on intestinal tumorigenesis in the ApcMin/+ mouse model. Furthermore, to explore the biological mechanisms by which estrogens may influence the pathogenesis of colorectal cancer, we performed gene expression profiles in colonocytes from ovariectomized wild‐type (WT) vs. ERβ−/− mice, treated with estradiol (E2) or vehicle. Specifically in female, ERβ deficiency was found to be associated with higher adenoma multiplicity in the small intestine, but not in the colon. Furthermore, tumors from ERβ−/−ApcMin/+ female mice were on average significantly larger than those from control ApcMin/+ mice. Higher steady‐state proliferation in epithelial cells of the jejunum and colon from ERβ−/−ApcMin/+ vs. ApcMin/+ female mice was confirmed by BrdU incorporation assay. Interestingly, functional categorization of microarray results revealed the TGFβ signaling pathway to be modulated in colonocytes, especially for the WT + E2 vs. WT + Vehicle and the ERβ−/− + E2 vs. WT + E2 comparisons. Using quantitative PCR analysis, we observed transcripts from ligands of the TGFβ pathway to be upregulated in colonocytes from E2‐treated WT and ERβ−/− mice and downregulated in ERβ‐deficient mice, mostly in an E2‐independent manner. Therefore, our results demonstrate that ERβ deficiency enhances small intestinal tumorigenesis and suggest that modulation of the TGFβ signaling pathway could contribute to the protective role of estrogens on intestinal tumorigenesis. © 2008 Wiley‐Liss, Inc.

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Is oestrogen receptor- β a predictor of endocrine therapy responsiveness in human breast cancer?

Cited by 69 publications

References 47 publications

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

ERβ in breast cancer—Onlooker, passive player, or active protector?

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice

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Is oestrogen receptor- β a predictor of endocrine therapy responsiveness in human breast cancer?

Cited by 69 publications

References 47 publications

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

ERβ in breast cancer—Onlooker, passive player, or active protector?

Estrogen receptor β deficiency enhances small intestinal tumorigenesis in ApcMin/+ mice

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Product

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Estrogen receptor β deficiency enhances small intestinal tumorigenesis in Apc^Min/+ mice