Abstract
Background: Estrogen and progesterone receptor (ER/PR) status is an accepted predictive marker in breast cancer. It is well known that breast tumors, which are ER(+) are more likely to respond to endocrine therapy. However, certain percentage of ER(+)/PR(+) tumors do not respond to endocrine therapy. Identification of the second estrogen receptor, named estrogen receptor beta (ER?), as well as the existence of numerous isoforms/splice variants of both ER? and ER?, suggests that complex regulation of estrogen action exists. In this study, we analyze does the expression of two ER? isoforms correlates with ER?/PR status. Methods: Sixty samples of primary operable breast carcinomas were analyzed for ER? and PR protein levels and for mRNA expression of two ER? isoforms (ER?1 and ER??5). ER? and PR proteins were measured by classical biochemical techniques, and ER? mRNAs were measured by real-time RT-PCR. Results: Tumors are divided in three groups according to relative level of mRNA for ER?1 and ER??5. We found that there is no correlation of ER?1 mRNA expression with ER? and PR protein levels. We confirmed the existence of inverse correlation of ER??5 with PR and of ER??5 with ER? in the group of postmenopausal patients. In the subsets of tumors defined by ER?/PR status, we found that percentage of tumors, which concomitantly expressed high levels of both transcripts, are parallel with those that do not response to tamoxifen treatment. Conclusion: Inverse correlation of ER? with ER??5 and PR with ER??5isoform suggests that ER??5 may have inhibitory effect on ER? activity in postmenopausal patients. In addition, we point out that determination of expression profiles of ER? and ER? isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance. .
Highlights
IntroductionEstrogen receptor (ER) status of breast tumor (expressed as + or – status) is a well-accepted predictor of response to endocrine therapy
Estrogen receptor (ER) status of breast tumor is a well-accepted predictor of response to endocrine therapy
EREP51$HQFRGHGWUXQFDWHGSURWHLQZLWKRXWOLJDQGELQGLQJGRPDLQ In examined samples of breast cancer (BC) we found that there are two groups, according to expression of ERE1 and EREi) those that are not different compared to normal mammary tissue (referred as ERE-positive or “high expressed” (Tu3)), Table 1, Figure 1 and 2.; ii) and those in which expression levels significantly varies from normal mammary tissue (referred as EREnegative or “medium expressed” (Tu2) and “low expressed” (Tu1)), Table 1, Figure 1 and 2
Summary
Estrogen receptor (ER) status of breast tumor (expressed as + or – status) is a well-accepted predictor of response to endocrine therapy. The exact biological significance of isoforms and its splice variants of both receptors (ERD and ERE), is still unclear, but it seems that their existence may have regulatory role in the response to estrogen. Both genes, ERD and ERE, have complex “system” of multiple promoters and differential splicing in 5’-UTR region [4]. We point out that determination of expression profiles of ERA and ERB isoforms in the defined groups of patient are necessary for elucidating its involvement in endocrine resistance
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