Increased expression of estrogen receptor beta mRNA in tamoxifen-resistantbreast cancer patients

Tamoxifen is currently the first-line therapy for treatment of hormone-depe ndent breast cancer. However, despite initial benefits, most patients event ually relapse. Two groups of patients were identified: (a) a tamoxifen-sens itive group (n = 8); and (b) a tamoxifen-resistant group (n = 9), Using rev erse transcription-PCR, the relative expression of mRNA for both estrogen r eceptor (ER) beta and transforming growth factor beta 1 was determined in e ach patient group and quantified against a known reference standard. ER-bet a mRNA was significantly up-regulated in the tamoxifen-resistant group as c ompared with the tamoxifen-sensitive group (P = 0.001 by Fisher's exact tes t), and, consistent with previous findings, transforming growth factor beta 1 was also up-regulated in the tamoxifen-resistant cohort (P = 0.02). The importance of ER-beta in tamoxifen resistance was validated using tamoxifen -sensitive and -resistant cell lines, in which it was demonstrated that ER- beta mRNA was significantly up-regulated in the resistant cells. These resu lts lend further support to a role for ER-beta as a poor prognostic factor in breast cancer.