Expression and promoter methylation status of OPCML andits functions in the inhibition ofcell proliferation, migration, and invasion in breast cancer.

Abstract

Opioid binding protein/cell adhesion molecule-like (OPCML) has been demonstrated to be a tumor suppressor gene, as it has been shown in previous studies to play a tumor-suppressive role in a variety of cancers. However, the role of OPCML in breast tumorigenesis remains unclear. In this study, we analyzed OPCML expression in breast cancers and adjacent non-tumor tissue samples and examined its molecular function in the breast cancer-derived cell lines MDA-MB-231 and MCF7. We found that OPCML was downregulated in most breast cancer samples but that this protein was expressed in most adjacent non-tumor samples. The loss or downregulation of OPCML is associated with hypermethylation of its promoter. Methylation of the OPCML promoter was detected in all breast cancer cell lines and primary tumors but was not detected in surgical margin tissues and normal breast tissues. Furthermore, functional assays showed that ectopic OPCML expression could inhibit breast tumor cell proliferation in vivo and in vitro and further suppresses tumor cell migration and invasion. Our results show that OPCML exerts its tumor-suppressive functions in human breast cancer cells. Moreover, the promoter-specific hypermethylation of OPCML plays an important role in human breast cancer development.