FUNCTIONAL ANALYSIS AND MECHANISTIC STUDY OF SETDB1 IN BREAST CANCER

Abstract

Emerging evidence shows deregulated histone methylation regulators involve in breast cancer progression. Histone H3K9 methyltransferase SETDB1 has been recently reported to involve in the malignancies of different cancers. Nevertheless, how SETDB1 functions to be an oncogene remains largely obscure. In breast cancer, we found that SETDB1 is recurrently amplified and abnormally expressed, which contributes to proliferation, colony formation and tumor growth of breast cancer cells. The behaviors of both wild-type and enzymatically-deficient SETDB1 in influencing clonogenic growth and regulating gene expression were investigated to identify the critical downstream pathway(s) and effector(s) for the oncogenic function of SETDB1, so as to provide evidence for the therapeutic rationale for targeting breast cancers with aberrantly expressed SETDB1.