Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer

Myers, E.; Fleming, Fergal J.; Crotty, Thomas B.; Kelly, Gabrielle; McDermott, E; O’Higgins, N.; Hill, A. D. K.; Young, Leonie S.

doi:10.1038/sj.bjc.6602156

Cited by 93 publications

(86 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In breast cancer patients treated with adjuvant TAM, high ERβ expression significantly correlates with increased overall [86,107] and disease-free survival [107], no disease progression [113], or no relapse within five years [93,114]. In patients treated with chemotherapy as well as TAM, ERβ expression also significantly correlates with increased OS [97,105] and DFS [94,97,104,105]. Higher ERβ expression is observed more frequently in TAM-sensitive breast tumors than in TAM-resistant tumors [113], and lower ERβ is associated with TAM resistance [107,113,114].…”

Section: Clinical Correlations Between Erβ Expression and Response Tomentioning

confidence: 98%

“…Thus, the number of tumors included in a study expressing ERβ only could influence the overall correlation with PR. ER expression may also correlate with expression of coregulatory proteins such as SRC-1, AIB1, and NCoR [92][93][94], and may impact therapeutic response. For example, high SRC-1 expression is associated positively with endocrine therapy resistance and inversely with ERβ expression [93,94].…”

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

confidence: 99%

“…ER expression may also correlate with expression of coregulatory proteins such as SRC-1, AIB1, and NCoR [92][93][94], and may impact therapeutic response. For example, high SRC-1 expression is associated positively with endocrine therapy resistance and inversely with ERβ expression [93,94]. However, there is no simple correlation for all coregulators, and changes in the overall ratio of coactivators to corepressors, or specific coactivators, may be most important [85].…”

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

confidence: 99%

“…In general, HER2 gene amplification and protein overexpression are inversely correlated with expression of ERα, or with ERα and ERβ together [63,90,[94][95][96][97]. Some ER+ tumors have been shown to have HER2 gene amplification, and patients treated with TAM whose tumors are HER2+/ER+ have poorer disease-free survival (DFS) and overall survival (OS) than those without HER2 [10,96].…”

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

confidence: 99%

“…We found fifteen studies investigating ERβ expression and response to endocrine therapy. Of these, thirteen examined ERβ protein expression using primarily IHC [82,86,87,93,94,97,104,105,107,[111][112][113][114]. Only three of these studies [82,97,107] separate ERβ tumor populations based on ERα status, although the majority of tumors typically contain both subtypes.…”

Section: Clinical Correlations Between Erβ Expression and Response Tomentioning

confidence: 99%

See 4 more Smart Citations

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

2008

View full text Add to dashboard Cite

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.

show abstract

Section: Clinical Correlations Between Erβ Expression and Response Tomentioning

confidence: 98%

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

confidence: 99%

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

confidence: 99%

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

confidence: 99%

Section: Clinical Correlations Between Erβ Expression and Response Tomentioning

confidence: 99%

See 3 more Smart Citations

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

2008

View full text Add to dashboard Cite

show abstract

Signalling by Steroid Receptors

Speirs¹

2007

The Cancer Handbook

View full text Add to dashboard Cite

Steroid hormones such as oestrogens control a wide variety of functions important for cell homeostasis, proliferation, differentiation, and apoptosis. Their action is mediated by specific hormone receptors, oestrogen receptor (ER)‐α and ERβ, which belong to a large superfamily of nuclear receptors. Typically, ERs function as ligand‐activated transcription factors, binding to specific oestrogen response elements (EREs) within target gene promoters and initiating a downstream response. Ligand‐independent gene transcription can also occur via tethered interactions with activating protein 1 (AP‐1) and stimulating protein 1 (SP1) proteins. A third pathway has been identified, involving membrane‐initiated signalling. These pathways are not mutually exclusive with evidence of considerable crosstalk between them. This chapter focuses on recent developments related to our understanding of these ER‐signalling mechanisms.

show abstract