The estrogen receptor variant lacking exon 5 (ERΔE5) 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 ERΔE5 in human breast epithelial cells has been studied by transient transfection of HMT-3522S1 cells with wild-type (wt) estrogen receptor (ER) and ERΔE5. A 10-fold higher expression of ERΔE5 mRNA compared to that of wt ER mRNA was found. However, the expression of ERΔE5 protein was significantly lower than the expression of wt ER protein. The ERΔE5 was unable to activate the transcription of an estrogen-responsive reporter gene in the absence as well as in the presence of estrogen. The ERΔE5 disclosed a dominant negative activity when expressed together with wt ER. These data indicate that the biological significance of ERΔE5 in human breast cancer is dubious.
Supported by the Danish Cancer Society and Lægeforeningens Forskningsfond/Højmosegård-legatet.