Identification of a novel human estrogen receptor-[alpha] splice variant able to enhance malignant biological behaviors of breast cancer cells

Since the early 1990s, multiple human estrogen receptor-[alpha] (hER-[alpha]) splice variants have been identified, of which the majority contain [greater than or equal to]1 deleted exon, and some are expressed as proteins with modified functions from the wild-type 66 kDa hER-[alpha] (ER- [alpha]66). In the present study, a novel hER-[alpha] splice variant, ER-[alpha]30, was identified and cloned from clinical breast cancer tissue. The ER-[alpha]30 sequence lacked a ligand-binding domain and a ligand-dependent transcriptional activation domain but retained the N-terminal transcriptional activation domain, the DNA-binding domain and a partial hinge domain, and possesses a unique 10-amino-acid domain. The expression of ER-[alpha]30 was associated with ER-[alpha]66-negative and progesterone receptor-negative breast cancer. The 30 kDa protein was expressed in stably transfected MDA-MB-231 cells, and the overexpression of ER-[alpha]30 in MDA-MB-231 cells enhanced malignant biological behaviors, including cellular proliferation, migration and invasion in vitro. The results of the present study indicated that ER-[alpha]30 might represent a potential biomarker for breast cancer. Key words: estrogen receptor-[alpha], splice variant, biological behaviours, breast cancer, MDA-MB-231 cells