In order to approach the molecular basis of the tissue-specific agonistic a
ctivity of antioestrogens, we have compared, at the mRNA level, the express
ion of various transcriptional cofactors (activators or repressors) of estr
ogen receptors in different breast (MCF7, ZR75-1, T47D, MDA-MB231) and endo
metrial (Ishikawa, RL-95-2 and HEC1A) human cancer cell lines. We showed th
at for SRC-1, CBP, TIF1 alpha, RIP140, N-CoR, and SMRT, no:significant: dif
ferences in the expression levels were observed between breast and endometr
ial cells. For TIF1 alpha mRNA, both isoforms were also detected at similar
levels in all the cells tested. By contrast, over-expression of AIB1 mRNA
was observed in MCF7 cells, but not in other breast or endometrial cells, i
rrespective: of their ER-status. We then used protein-protein interaction a
ssay (far-Western blot) to confirm the increased expression of at least one
of the p160 proteins in MCF7 cells. Finally, we demonstrated that RIP140 m
RNA is directly induced by estrogens in ER-positive MCF7 breast cancer cell
lines but not in Ishikawa endometrial cells. Together these results indica
te that some differences exist between breast and endometrial cancer cell l
ines at the level of estrogen receptor transcription cofactor expression. (
C) 1999 Elsevier Science Ireland Ltd. All rights reserved.