Expression of estrogen receptor beta wt isoform (ER beta 1) and ER beta Delta 5 splice variant mRNAs in sporadic breast cancer
Tanić, Nikola T
Nešković-Konstantinović, Zora B.
Celeketić, Dusica C
Dimitrijević, Bogomir B.
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Purpose In addition to Estrogen Receptor alpha (ER alpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ER beta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. Methods In this study, the expression of ER beta 1 mRNA (wild type of beta receptor) and splice variant ER beta Delta 5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ER alpha and PR protein levels and with clinical and histopathological parameters. Results We found the inverse correlation of ER beta Delta 5 mRNA expression with the levels of PR and ER alpha proteins in the group of postmenopausal patients; we also report the lower expression of ER beta 1 and ER beta Delta 5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (<= 20 mm, T1). The decrease of ER beta Delta 5 mRNA expression in larger tumors is found to arise from ER-positive breast carcinomas. In addition, the portion of tumors with concomitant high expression of both transcripts matches up the known percentage of tumors resistant to endocrine therapy in patients with different ER/PR status. Conclusions As far as we know, this is the first study in which ER beta Delta 5 mRNA splice variant was quantified by realtime RT-PCR in the clinical samples of breast cancer tissue. Until now, the focus of clinical reports was the level of ER beta 1, ER beta 2, and ER beta 5 isoforms. The higher expression of ER beta Delta 5 mRNA is associated with the indicators of low biological aggressiveness of tumor (low tumor size within ER-positive status in our study) suggesting that the uncontrolled local tumor growth may occur as the expression of ER beta Delta 5 mRNA decreases in estrogen-dependent breast cancer.