Prognostic Significance of TRIM24/TIF-1α Gene Expression in Breast Cancer

Abstract

In this study, we have analyzed the expression of TRIM24/TIF-1␣, a negative regulator of various transcription factors (including nuclear receptors and p53) at the genomic, mRNA, and protein levels in human breast tumors. In breast cancer biopsy specimens, TRIM24/TIF-1␣ mRNA levels (assessed by Real-Time Quantitative PCR or microarray expression profiling) were increased as compared to normal breast tissues. At the genomic level, array comparative genomic hybridization analysis showed that the TRIM24/TIF-1␣ locus (7q34) exhibited both gains and losses that correlated with mRNA levels. By re-analyzing a series of 238 tumors, high levels of TRIM24/TIF-1␣ mRNA significantly correlated with various markers of poor prognosis (such as the molecular subtype) and were associated with worse overall survival. By using a rabbit polyclonal antibody for immunochemistry, the TRIM24/TIF-1␣ protein was detected in nuclei of normal luminal epithelial breast cells, but not in myoepithelial cells. Tissue microarray analysis confirmed that its expression was increased in epithelial cells from normal to breast infiltrating duct carcinoma and correlated with worse overall survival. Altogether, this work is the first study that shows that overexpression of the TRIM24/TIF-1␣ gene in breast cancer is associated with poor prognosis and worse survival, and it suggests that this transcription coregulator may play a role in mammary carcinogenesis and represent a novel prognostic marker.

TRIM24 promotes the aggression of gastric cancer via the Wnt/β-catenin signaling pathway

“…The overexpression of TRIM24 has been reported in several types of human tumor, and has been associated with increased malignant behavior and poor prognosis in cancer, including hepatocellular carcinoma (19), breast cancer (25), head and neck squamous cell carcinoma (26), glioma (27) non-small cell lung cancer (28) and bladder cancer (29). In the present study, the immunohistochemical analysis showed that TRIM24 was significantly overexpressed in GC tissues.…”

Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor

“…31 The C-terminal PHD-bromo domain of TRIM24 acts as a dual “reader” of unmodified H3K4 and acetylated H3K23 marks within the same histone tail, 32 additionally, TRIM24 can also bind to non-histone KAc marks on other proteins, including p53. 33 Genetic knock-down of TRIM24 in cancer cells results in antiproliferative phenotypes, and overexpression of TRIM24 has also been linked to poor prognosis for several cancers, including breast, 32, 34 head and neck, 35 non-small cell lung, 36 hepatocellular, 37 and glioblastoma. 38 Because of the interest in TRIM24 here at MD Anderson and the druggability of BCPs, 18 we set out to develop a potent (cellular EC 50 < 100 nM) and selective TRIM24 chemical probe in order to interrogate the role of the bromodomain in human disease.…”

Limiting the power of p53 through the ubiquitin proteasome pathway

“…For example, Trim24 overexpression in immortalized human mammary epithelial cells reduces p53 levels dramatically (Pathiraja et al 2014). TRIM24 is overexpressed in breast cancer and other human tumors (Tsai et al 2010;Chambon et al 2011). A recent study provides evidence that Trim24 prefers phosphorylated p53 for targeting (Jain et al 2014).…”