Estrogen Receptor β Is Coexpressed with ERα and PR and Associated with Nodal Status, Grade, and Proliferation Rate in Breast Cancer

Järvinen, Tero A.H.; Pelto‐Huikko, Markku; Holli, Kaija; Isola, Jorma

doi:10.1016/s0002-9440(10)64702-5

Cited by 261 publications

(256 citation statements)

References 18 publications

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“…In their study they used frozen sections of tissue and found that only 59% (52 out of 88) were positive for ERb, with only 38% of the ERa negative samples expressing the ERb subtype. This proportion is much lower than in the current study or in the tissue set studied by Jarvinen et al (2000) who used frozen sections fixed briefly with Zamboni's, and found 60% of cancers contained ERb1 positive cells using a commercial polyclonal antibody raised to the same region of the protein. The need to use frozen sections clearly limits the utility of these antibodies and highlights an important difference with the reagent used in the present study which appears capable of identifying ERb1 in material fixed by formalin, methacarn (unpublished observations) or Bouins (Saunders et al, 2000).…”

Section: Molecular and Cellular Pathologycontrasting

confidence: 71%

“…We have detected cytoplasmic staining using some commercial anti ERb antibodies especially those that have not been affinity purified and with some secondary antibodies especially those raised in goats (unpublished observations). These findings may explain some of the cytoplasmic staining seen in the figures published by others (Jarvinen et al, 2000;Mann et al, 2001;Omoto et al, 2001). …”

Section: Molecular and Cellular Pathologysupporting

confidence: 53%

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Expression of oestrogen receptor beta (ERβ1) protein in human breast cancer biopsies

et al. 2002

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Oestrogen action is mediated via specific receptors that act as ligand-activated transcription factors. A monoclonal antibody specific to the C-terminus of human oestrogen receptor beta has been characterized and the prevalence of expression of oestrogen receptor beta protein investigated in a well defined set of breast cancers. Reverse transcription-polymerase chain reaction analysis of RNA from tissue biopsies detected oestrogen receptor beta in all samples examined. The anti-oestrogen receptor beta antibody cross reacted specifically with both long (*59 Kd) and short (*53 Kd) forms of recombinant oestrogen receptor beta. Western blot analysis of breast tumours contained both forms of oestrogen receptor beta protein although in some samples lower molecular weight species (32 -45 Kd) were identified. Fifty-one breast cancer biopsies were examined using immunohistochemistry; 41 (80%) were immunopositive for oestrogen receptor alpha, 48 (94%) were immunopositive for oestrogen receptor beta and 38 (74.5%) co-expressed both receptors. Expression of oestrogen receptor beta was exclusively nuclear and occurred in multiple cell types. There was no quantitative relationship between staining for the two ERs although in tumours in which both receptors were present immunoexpression of oestrogen receptor alpha was invariably more intense. The significance of oestrogen receptor beta protein expression in breast cancers to therapy remains to be determined but the availability of a well characterized antibody capable of detecting oestrogen receptor beta in archive material will facilitate the process.

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Section: Molecular and Cellular Pathologycontrasting

confidence: 71%

Section: Molecular and Cellular Pathologysupporting

confidence: 53%

Expression of oestrogen receptor beta (ERβ1) protein in human breast cancer biopsies

et al. 2002

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“…DCIS lesions have reduced ERβ expression compared with normal epithelium, with high-grade DCIS showing the most significant reduction [61]. Invasive breast carcinomas tend to have lower levels of ERα and ERβ than DCIS, but approximately two-thirds of the tumors are still positive by IHC [63]. Interestingly, hypermethylation of one of two ERβ promoters was observed in cell lines and tumors, and correlated with decreased ERβ expression [64].…”

Section: Erα and Erβ Expression And Activitiesmentioning

confidence: 99%

“…To date, it appears that ERα expression is increased and ERβ expression is decreased in early breast cancers, whereas expression of both receptors declines in more invasive cancers [61][62][63]. This correlates with the loss of ERβ preferentially in other cancers compared to normal tissue, and led to the hypothesis that ERβ is a tumor suppressor [65,66].…”

Section: Erα and Erβ Expression And Activitiesmentioning

confidence: 99%

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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“…The second receptor, ER, has likewise been detected in human breast cancers and may also contribute to hormonal sensitivity and resistance [47][48][49]. The clinical assay of this receptor has not been performed in large series.…”

Section: Expression Of Estrogen Receptor mentioning

confidence: 99%

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Platet

Cathiard

Gleizes

et al. 2004

Critical Reviews in Oncology/Hematology

317

236

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Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ER and ERIn this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to metastasis, and of their clinical consequences in the prevention, prognosis and treatment of the disease. The requirement of estrogen receptors, mainly of the alpha subtype, in normal mammary gland differentiation and growth has been evidenced by estrogen receptor deficiency in animals. The promotion of breast cancer carcinogenesis by prolonged exposure to estrogens is well-documented and this has logically led to the use of antiestrogens as potentially chemopreventive agents. In breast cancer progression, however, the exact roles of estrogen receptors have been less well established but they may possibly be dual. Estrogens are mitogenic in ER-positive cells and antiestrogens are an efficient adjuvant therapy for these tumors. On the other hand, the fact that estrogens and their receptors protect against cancer cell invasiveness through distinct mechanisms in experimental models may explain why the presence of ER is associated with well-differentiated and less invasive tumors.2

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Estrogen Receptor β Is Coexpressed with ERα and PR and Associated with Nodal Status, Grade, and Proliferation Rate in Breast Cancer

Cited by 261 publications

References 18 publications

Expression of oestrogen receptor beta (ERβ1) protein in human breast cancer biopsies

Expression of oestrogen receptor beta (ERβ1) protein in human breast cancer biopsies

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

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

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