title: Estrogen receptor β agonists affect growth and gene expression of human breast cancer cell lines.
abstract: Expression of estrogen receptor β (ERβ) has been described to reduce growth of cancer cell lines derived from hormone-dependent tumors, like breast cancer. In this study we tested to what extent two ERβ agonists, androgen derivative 3β-Adiol and flavonoid Liquiritigenin, would affect growth and gene expression of different ERβ-positive human breast cancer cell lines. Under standard cell culture conditions, we observed 3β-Adiol to inhibit growth of MCF-7 cells in a dose-dependent manner, whereas growth of BT-474 and MCF-10A cells was suppressed by the maximum concentration (100 nM) only. When treated in serum-free medium, all cell lines except of MDA-MB-231 were responsive to 1 nM 3β-Adiol, and ZR75-1 cells exhibited a dose-dependent antiproliferative response. Providing putative mechanisms underlying the observed growth-inhibitory effect, expression of Ki-67 or cyclins A2 and B1 was downregulated after 3β-Adiol treatment in all responsive lines. In contrast, treatment with lower doses of Liquiritigenin did not affect growth. In MCF-7 cells, the highest dose of this flavonoid exerted proliferative effects accompanied by increased expression of cyclin B1, PR and PS2, indicating unspecific activation of ERα. In conclusion, the ERβ agonists tested exerted distinct concentration-dependent and cell line-specific effects on growth and gene expression. The observed inhibitory effects of 3β-Adiol on breast cancer cell growth encourage further studies on the potential of this and other ERβ agonists as targeted drugs for breast cancer therapy.
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Regensburg, Regensburg, Germany. claus.lattrich@klinik.uni-regensburg.de
authors.forename: Claus
authors.initials: C
authors.lastname: Lattrich
authors.forename: Anette
authors.initials: A
authors.lastname: Stegerer
authors.forename: Julia
authors.initials: J
authors.lastname: Häring
authors.forename: Susanne
authors.initials: S
authors.lastname: Schüler
authors.forename: Olaf
authors.initials: O
authors.lastname: Ortmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Treeck
mesh_terms: D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics; D015113:Androstane-3,17-diol / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D013997:Time Factors
chemical_list: D056744:Cyclin B1; D047629:Estrogen Receptor beta; D044950:Flavanones; D015113:Androstane-3,17-diol; C083152:liquiritigenin