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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 (ERdeltaE5) encodes a truncated protein that lacks the hormone-binding domain and has been suggested to be responsible for the estrogen-independent growth of human breast tumors and resistance to antiestrogen therapy. The biological function of the ERdeltaE5 in human breast epithelial cells has been studied by transient transfection of HMT-3522S1 cells with wild-type (wt) estrogen receptor (ER) and ERdeltaE5. A 10-fold higher expression of ERdeltaE5 mRNA compared to that of wt ER mRNA was found. However, the expression of ERdeltaE5 protein was significantly lower than the expression of wt ER protein. The ERdeltaE5 was unable to activate the transcription of an estrogen-responsive reporter gene in the absence as well as in the presence of estrogen. The ERdeltaE5 disclosed a dominant negative activity when expressed together with wt ER. These data indicate that the biological significance of ERdeltaE5 in human breast cancer is dubious.