Abstract 1144: Overexpression of Tripartite Motif-containing 24 contributes to human epithelium cell carcinoma and correlates with poor prognosis of patient with local advanced head and neck squamous cell carcinoma

Abstract

Abstract BACKGROUND: To identify new and useful candidate biomarkers in head and neck squamous cell carcinoma (HNSCC), we performed a genome-wide survey and found that Tripartite motif-containing 24(TRIM24) was a gene that was markedly up-regulated in HNSCC. TRIM24 is a member of transcriptional intermediary factor 1 family, functions as a co-regulator that modulate transcriptional activities of several nuclear receptors, either positively or negatively. Here, we investigated the effects of TRIM24 on proliferation, invasion and apoptotic potential in HNSCC cell lines as well as its clinical significance in HNSCC. METHODS: The expressions of TRIM24 were examined through real-time PCR and western blot in 56 pairs of HNSCC and adjacent normal samples, as well as in 8 HNSCC cell lines and primary normal keratinocytes. Three TRIM24 high-expressed cell line were transfected with TRIM24 siRNA, then the proliferation, invasion and apoptotic potential was assessed by cell-counting kit-8, colony formation, matrigel invasion chambers and flow cytometry. In addition, the clinical implication of TRIM24 was investigated in another independent 91 locally advanced HNSCC by immunohistochemistry. RESULTS: TRIM24 mRNA expression were up-regulated remarkably in HNSCC samples and cell lines through real-time PCR. Correspondingly, elevated TRIM24 translation levels were found in 2 of 3 (67%) HNSCC tissues that were selected randomly from the 56 paired HNSCC tissues and 6 of 8 HNSCC cell lines using Western blot analysis. A significant reduction in cell proliferation and increase in population of apoptotic cells were observed in TRIM24 siRNA transfected cell lines in p53-dependent manner. Moreover, 55%(50/91) of HNSCC samples show high expression of TRIM24 by immunohistochemistry and survival analyses indicated a significant association between TRIM 24 high expression and a reduced overall survival in patients with locally advanced HNSCC (log rank test, P = 0.020). CONCLUSION: Our data indicated that overexpression of TRIM24 may play an important role in HNSCC tumorigenesis and serve as an independent prognostic predictor for patients with locally advanced HNSCC. ACKNOWLEDGMENTS: This study was supported by the National Natural Science Foundation of China (Grant No. 30973343), Projects of the Shanghai Science and Technology Committee (Grant No. 08JC1414400 and 10XD1402500) and the Shanghai Leading Academic Discipline Project (S30206). *Yan Lu and Wei Cao contributed equally to this work. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1144. doi:1538-7445.AM2012-1144