GSE125902
Identification of HOXB13 binding sites in metastatic PC treated with Enzalutamide
HOXB13 is a developmentally regulated transcription factor, co-expressed along with the   Androgen receptor (AR) in a majority of PCs. Previous studies have indicated context dependent   roles of HOXB13 in the functional regulation of AR and enrichment of HOXB13 motifs in the AR   cistrome. Our studies showed that genetic or pharmacological blockade of HOXB13   sensitized mCRPCs to Enzalutamide (ENZ, Xtandi), an anti-androgen that is currently   deployed to treat mCRPC patients. To identify HOXB13-mediated mechanism of   castration-resistance ChIP-sequencing was  performed with the HOXB13-K13ac,  or IgG antibodies   in the metastatic prostate cancer cell line, C4-2B in vehicle treated as well as Enzalutamide  treated cell lines. We demonstrated for the first time  that BRD4, epigenetically regulates HOXB13  gene expression in PCs. Consistently, JQ1 the prototype BET inhibitor suppresses   HOXB13 expression and inhibit mCRPC growth. ChIP-sequence analysis reveals that  HOXB13 recruitment to the chromatin is not completely abrogated in Enzalutamide treated  cells identify a subset of genes that may have potential role in CRPC proliferation, anti-androgen   resistance and metastasis. Overall design: Six samples were analyzed. These samples included Vehicle control for the inhibitor treatments and IgG  for antibody control. treaan be targeted with MA4--022-1