Identification of a novel human estrogen receptor-αsplice 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 >= 1 deleted exon, and some are expressed as proteins with modified functions from the wild-type 66 kD alpha 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.