THE ESTROGEN-RECEPTOR VARIANT LACKING EXON-5 HAS DOMINANT-NEGATIVE ACTIVITY IN THE HUMAN BREAST EPITHELIAL-CELL LINE HMT-3522S1

The estrogen receptor variant lacking exon 5 (ER Delta E5) encodes a t runcated protein that lacks the hormone-binding domain and has been su ggested to be responsible for the estrogen-independent growth of human breast tumors and resistance to antiestrogen therapy. The biological function of the ER Delta E5 in human breast epithelial cells has been studied by transient transfection of HMT-3522S1 cells with wild-type ( wt) estrogen receptor (ER) and ER Delta E5. A 10-fold higher expressio n of ER Delta E5 mRNA compared to that of wt EPI mRNA was found, Howev er, the expression of ER Delta E5 protein was significantly lower than the expression of wt ER protein. The ER Delta E5 was unable to activa te the transcription of an estrogen-responsive reporter gene in the ab sence as well as in the presence of estrogen, The ER Delta E5 disclose d a dominant negative activity when expressed together with wt ER, The se data indicate that the biological significance of ER Delta E5 in hu man breast cancer is dubious.