Expression of Estrogen Receptor-β in Normal Mammary and Tumor Tissues: is it Protective in Breast Carcinogenesis?

Park, Byeong Woo; Kim, Ki Suk; Heo, Min Kyu; Ko, Seung Sang; Hong, Soon Won; Yang, Woo Ick; Kim, Joo Hang; Kim, Gwi Eon; Lee, Kyong Sik

doi:10.1023/a:1024406223619

Cited by 60 publications

(49 citation statements)

References 16 publications

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“…Instead, decreased expression of ERb was observed in cells with forced expression of ARTN. Several reports have described loss of ERb during mammary tumorigenesis, supporting the potential role of ERb as a tumor suppressor (Park et al, 2003;Shaaban et al, 2003;Bardin et al, 2004;Rody et al, 2005). ERb has been reported to modulate ERa activity and cellular response to estrogen (Hall and McDonnel, 1999;Pettersson et al, 2000).…”

Section: Discussionmentioning

confidence: 85%

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: 85%

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

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“…Estrogen receptor b (ER b) expression was observed to be significantly decreased in breast cancer and metastatic lymph node tissues compared with normal mammary and benign breast tumors (Park et al, 2003). An inverse relationship was found between ER b mRNA level and both histologic grade and progesterone receptor expression.…”

Section: Discussionmentioning

confidence: 99%

Prediction of high risk Ewing's sarcoma by gene expression profiling

et al. 2004

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Ewing's sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Currently accepted clinical prognostic factors fail to classify ES patients' risk to relapse at diagnosis. We aimed to find a new strategy to distinguish between poor and good prognosis ES patients already at diagnosis. We analysed the gene expression profiles of 14 primary tumor specimens and six metastases from ES patients, using oligonucleotide microarray analysis. The over-expression of two genes was validated by quantitative PCR using the LightCycler system. We identified two distinct gene expression signatures distinguishing high-risk ES patients that are likely to progress from low-risk ES patients with a favorable prognosis of long-term progression-free survival. The microarray-based classification was superior to currently used prognostic parameters. Over-expressed genes in the poor prognosis patients included genes regulating the cell cycle and genes associated with invasion and metastasis, while among the downregulated genes were tumor suppressor genes and inducers of apoptosis. Our results indicate the existence of a specific gene expression signature of outcome in ES already at diagnosis, and provide a strategy to select patients who would benefit from risk-adapted improved therapy.

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“…ERb expression was decreased in BC and metastatic lymph node tissues as compared with normal mammary and benign breast tumor (BBT) tissues. The intensity and extent of ERb expression were significantly higher in normal and BBT tissues than in BC or metastatic lymph node tissues (Park et al 2003).…”

Section: Analysis Of Era and Erb Expression In Estrogen-sensitive Canmentioning

confidence: 86%

“…Similar findings were obtained at the mRNA level by the RT-PCR method by Iwao et al (2000), who also showed that ERa mRNA is increased and ERb mRNA decreased during breast carcinogenesis. Recently, Park et al (2003) compared ERb mRNA levels in various breast tissues, using mRNA in situ hybridization. ERb expression was decreased in BC and metastatic lymph node tissues as compared with normal mammary and benign breast tumor (BBT) tissues.…”

Section: Analysis Of Era and Erb Expression In Estrogen-sensitive Canmentioning

confidence: 99%

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

Bardin¹,

Boulle²,

Lazennec³

et al. 2004

Endocr Relat Cancer

386

308

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The characterization of estrogen receptor beta (ERb) brought new insight into the mechanisms underlying estrogen signaling. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues, and the mitogenic effects of estrogen in these tissues (such as breast, endometrium and ovary) are well documented both in vitro and in vivo. There is also an emerging body of evidence that colon and prostate cancer growth is influenced by estrogens. In all of these tissues, most studies have shown decreased ERb expression in cancer as compared with benign tumors or normal tissues, whereas ERa expression persists. The loss of ERb expression in cancer cells could reflect tumor cell dedifferentiation but may also represent a critical stage in estrogen-dependent tumor progression. Modulation of the expression of ERa target genes by ERb or ERb-specific gene induction could explain that ERb has a differential effect on proliferation as compared with ERa. ERb may exert a protective effect and thus constitute a new target for hormone therapy, such as ligand specific activation. The potential distinct roles of ERa and ERb expression in carcinogenesis, as suggested by experimental and clinical data, are discussed in this review.

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Expression of Estrogen Receptor-β in Normal Mammary and Tumor Tissues: is it Protective in Breast Carcinogenesis?

Cited by 60 publications

References 16 publications

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

Prediction of high risk Ewing's sarcoma by gene expression profiling

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

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