FUNCTIONAL STUDIES OF ER60 PROTEASE IN BREAST CANCER

Abstract

ER60 protease (also known as ER60) is a luminal protein of the endoplasmic reticulum and member of the disulfide isomerase protein family. It is an important chaperone protein involved in the quality control of nascent glycoproteins. ER60 has been previously reported to be over-expressed in breast cancer but its functions in breast cancer remain unknown. In this study, silencing of the ER60 gene in two breast cancer cell lines reduced cell proliferation and induced G1/S arrest, while ER60 over-expression resulted in higher cell proliferation. ER60-silenced MDA-MB-231 cells were also found to have significantly inhibited tumor formation in immunodeficient SCID mice. In clinical breast cancer samples, ER 60 showed positive correlation with proliferation, tumor size, cancer stage, lymph node status and distant metastasis . A genome-wide cDNA microarray analysis was performed to elucidate the possible molecular pathways involved. It appears that ER60 protease plays an important role in breast carcinogenesis.