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  • The c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis.

The c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis.

The Journal of pathology (2018-06-22)
Jin-Fen Xiao, Qiao-Yang Sun, Ling-Wen Ding, Wenwen Chien, Xin-Yu Liu, Anand Mayakonda, Yan-Yi Jiang, Xin-Yi Loh, Xue-Bin Ran, Ngan B Doan, Brandon Castor, David Chia, Jonathan W Said, Kar Tong Tan, Henry Yang, Xin-Yuan Fu, De-Chen Lin, H Phillip Koeffler
ABSTRACT

Characterising the activated oncogenic signalling that leads to advanced breast cancer is of clinical importance. Here, we showed that SET domain, bifurcated 1 (SETDB1), a histone H3 lysine 9 methyltransferase, is aberrantly expressed and behaves as an oncogenic driver in breast cancer. SETDB1 enhances c-MYC and cyclin D1 expression by promoting the internal ribosome entry site (IRES)-mediated translation of MYC/CCND1 mRNA, resulting in prominent signalling of c-MYC to promote cell cycle progression, and provides a growth/self-renewal advantage to breast cancer cells. The activated c-MYC-BMI1 axis is essential for SETDB1-mediated breast tumourigenesis, because silencing of either c-MYC or BMI1 profoundly impairs the enhanced growth/colony formation conferred by SETDB1. Furthermore, c-MYC directly binds to the SETDB1 promoter region and enhances its transcription, suggesting a positive regulatory interplay between SETDB1 and c-MYC. In this study, we identified SETDB1 as a prominent oncogene and characterised the underlying mechanism whereby SETDB1 drives breast cancer, providing a therapeutic rationale for targeting SETDB1-BMI1 signalling in breast cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Anti-SETDB1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Hydrogen peroxide solution, 30 % (w/w) in H2O, contains stabilizer
Sigma-Aldrich
TWEEN® 20, for molecular biology, viscous liquid