Identification of a novel human estrogen receptor-α splice variant

Since the early 1990s, multiple human estrogen receptor-α (hER-α) 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 kDa hER-α (ER-α66). In the present study, a novel hER-α splice variant, ER-α30, was identified and cloned from clinical breast cancer tissue. The ER-α30 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‐α30 was associated with ER-α66-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‐α30 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-α30 might represent a potential biomarker for breast cancer.