ER81-shRNA inhibits growth of triple-negative human breast cancer cell line MDA-MB-231 in vivo and in vitro.

Thelackofeffectivetreatmenttargetsfortriple-negativebreastcancersmakethemunfittedforendocrine� or HER2 targeted therapy, and their prognosis is poor. Transcription factor ER81, a downstream gene of the HER2, is highly expressed in breast cancer lines, breast atypical hyperplasia and primary breast cancers including triple-negative examples. However, whether and how ER81 affects breast cancer carcinogenesis have remained elusive.�Wehereassessedinfluenceonatriple-negativecellline.�ER81-shRNAwasemployedtosilenceER81� expressionintheMDA-MB-231�cellline,�andMTT,�colony-formingassays,�andflowcytometrywereusedtodetect� cell proliferation, colony-forming capability, cell cycle distribution, and cell apoptosis in vitro. MDA-MB-231 cellsstablytransfectedwithER81-shRNAwereinoculatedintonudemice,�andgrowthinhibitionofthecells� wasobservedinvivo.�WefoundthatER81�mRNAandproteinexpressioninMDA-MB-231�cellswasnoticeably� reducedbyER81-shRNA,�andthatcellproliferationandclonalityweredecreasedsignificantly.� ER81-shRNA� further increased cell apoptosis and the residence time in G 0 /G 1 phase, while delaying tumor-formation and growth rate in nude mice. It is concluded that ER81 may play an important role in the progression of breast cancer and may be a potentially valuable target for therapy, especially for triple negative breast cancer.