Expression of nuclear receptor interacting proteins TIF-1, SUG-1, receptorinteracting protein 140, and corepressor SMRT in tamoxifen-resistant breast cancer

Regulation of gene transcription as a consequence of steroid receptor-DNA i nteraction is mediated via nuclear receptor interacting proteins (RIPs), in cluding coactivator or corepressor proteins, which interact with both the r eceptor and components of the basic transcriptional unit and vary between c ell types. The aim of this study was to test the hypothesis that resistance of some breast carcinomas to tamoxifen was associated with inappropriate e xpression of some of these RIPs, Using Northern analysis, we observed no si gnificant difference between the amount of either TIF-1 or SUG-1 mRNA expre ssed in parental MCF-7 and MCF-7 tamoxifen-resistant cell Lines. However, t he expression of RIP140 mRNA was lower in the resistant cell line and in th e presence of estradiol, the level of RIP140 mRNA was higher in the resista nt cells but not in the parental cells. In a cohort of 19 tamoxifen-resista nt breast tumor samples, there was no significant difference in the level o f the RIP140 and TIF-1 and corepressor SMRT mRNA compared with tamoxifen-tr eated tumors (II = 6) or untreated tumors (n = 21), However, SUG-1 mRNA was lower in resistant breast tumors. These data provide no support for increa sed expression of these RIPs or decreased expression of corepressor SMRT fo r being a mechanism for resistance of breast tumors to tamoxifen.