Treeck, Oliver and Juhasz-Boess, Ingolf and Lattrich, Claus and Horn, Felicitas and Goerse, Regina and Ortmann, Olaf (2008) Effects of exon-deleted estrogen receptor beta transcript variants on growth, apoptosis and gene expression of human breast cancer cell lines. BREAST CANCER RESEARCH AND TREATMENT, 110 (3). pp. 507-520. ISSN 0167-6806, 1573-7217
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Estrogen receptor beta gene codes for a variety of transcript isoforms resulting from alternative splicing, which are expressed both in mammary gland and in breast cancer cells. We studied the function of two exon-deleted ER beta isoforms recently identified by our group in comparison to ER beta 1 in regulation of growth, apoptosis and gene expression of two breast cancer cell lines with different ER alpha status. Overexpression of ER beta 1, but not of the exon-deleted variants exerted strong antitumoral effects both on ER alpha-positive MCF-7 and ER alpha-negative SK-BR-3 cells. ER beta 1 overexpression slowed growth of MCF-7 and SK-BR-3 cells in the absence of E2 and also inhibited E2-triggered growth stimulation of MCF-7 cells, but overexpression of the exon-skipped variants did not affect cell growth. Whereas overexpression of ER beta 1 triggered an increased basal and tamoxifen-induced apoptosis of MCF-7 and SK-BR-3 cells, the isoforms ER beta delta 125 or ER beta delta 1256 did not affect cellular tamoxifen response. The observed lack of function of the exon-deleted variants in terms of regulation of proliferation was accompanied both by their inability to affect expression of cyclins D1 and A2, p21 (WAF1) and PR and their disability to modulate estrogen response element (ERE) activation. In contrast, our results demonstrating antitumoral effects of ER beta 1 on breast cancer cells with different ER alpha-status support the hypothesis that ER beta is able to exert antitumoral actions both on ER alpha-positive and -negative breast cancer cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESSENGER-RNA EXPRESSION; ER-ALPHA; CYCLE PROGRESSION; WILD-TYPE; ANTIESTROGEN REGULATION; OSTEOSARCOMA CELLS; SPLICE VARIANTS; MAMMARY-GLAND; PROLIFERATION; IDENTIFICATION; estrogen receptor beta; splice variant; breast cancer cell; proliferation; estradiol; tamoxifen; gene expression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 15:32 |
| Last Modified: | 26 Oct 2020 15:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30500 |
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