Abstract
BackgroundEstrogen receptor alpha36 (ERalpha36), a variant of estrogen receptor alpha (ER) is expressed in about half of breast tumors, independently of the [ER+]/[ER-] status. In vitro, ERalpha36 triggers mitogenic non-genomic signaling and migration ability in response to 17beta-estradiol and tamoxifen. In vivo, highly ERalpha36 expressing tumors are of poor outcome especially as [ER+] tumors are submitted to tamoxifen treatment which, in turn, enhances ERalpha36 expression.ResultsOur study aimed to validate ERalpha36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent proliferative tumor toward an estrogen dispensable metastatic disease. In a retrospective study, we tried to decipher underlying mechanisms of cancer progression by using an original modeling of the relationships between ERalpha36, other estrogen and growth factor receptors and metastatic marker expression. Nonlinear correlation analyses and mutual information computations led to characterize a complex network connecting ERalpha36 to either non-genomic estrogen signaling or to metastatic process.ConclusionsThis study identifies ERalpha36 expression level as a relevant classifier which should be taken into account for breast tumors clinical characterization and [ER+] tumor treatment orientation, using a generic approach for the rapid, cheap and relevant evaluation of any candidate gene expression as a predictor of a complex biological process.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-015-0178-7) contains supplementary material, which is available to authorized users.
Highlights
Estrogen receptor alpha36 (ERalpha36), a variant of estrogen receptor alpha (ER) is expressed in about half of breast tumors, independently of the [ER+]/[ER-] status
ER-positive/ negative ([ER+]/[ER-]) status refers to the expression of the 66kDa nuclear estrogen receptor α (ERα66) in tumors, which are cured by endocrine therapeutic
In the present study, we examined Estrogen receptor alpha 36 (ERα36) expression in breast tumor specimens from 118 patients
Summary
Estrogen receptor alpha (ERalpha36), a variant of estrogen receptor alpha (ER) is expressed in about half of breast tumors, independently of the [ER+]/[ER-] status. Breast tumors are usually classified according to clinical parameters (size, grade, lymph node extension) and molecular expression status (ER, PR, HER2, Claudin) [1]. Such a classification allows clinicians ordering the appropriate treatment. ERα36 is generated from a promoter located in the first intron of the ESR1 gene, indicating that ERα36 expression is regulated independently from ERα66 This is Chamard-Jovenin et al BMC Systems Biology (2015) 9:28 consistent with the finding that ERα36 protein is present in about 40 % of [ER+] and [ER-] breast tumors
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