Effects of exon-deleted estrogen receptor beta transcript variants on growth, apoptosis and gene expression of human breast cancer cell lines.
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 ERbeta isoforms recently identified by our group in comparison to ERbeta1 in regulation of growth, apoptosis and gene expression of two breast cancer cell lines with different ERalpha status. Overexpression of ERbeta1, but not of the exon-deleted variants exerted strong antitumoral effects both on ERalpha-positive MCF-7 and ERalpha-negative SK-BR-3 cells. ERbeta1 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 ERbeta1 triggered an increased basal and tamoxifen-induced apoptosis of MCF-7 and SK-BR-3 cells, the isoforms ERbetadelta125 or ERbetadelta1256 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 ERbeta1 on breast cancer cells with different ERalpha-status support the hypothesis that ERbeta is able to exert antitumoral actions both on ERalpha-positive and -negative breast cancer cells.
Treeck
Oliver
O
Department of Obstetrics and Gynecology, University of Regensburg, Landshuter Str. 65, 93053 Regensburg, Germany. otreeck@caritasstjosef.de
Juhasz-Boess
Ingolf
I
Lattrich
Claus
C
Horn
Felicitas
F
Goerse
Regina
R
Ortmann
Olaf
O
D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020218:Response Elements / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D047629:Estrogen Receptor beta; D020033:Protein Isoforms; D012333:RNA, Messenger