Abstract 1510: Different change of LEF1/TCFs family members in colorectal carcinogenesis.

Abstract Wnt/β-catenin pathway is activated in many cancers, especially colorectal carcinoma (CRC). LEF1/TCFs family, which includes LEF1, TCF7(TCF1), TCF7L1(TCF3) and TCF7L2(TCF4), are required for β-catenin-induced transcription of target genes which are widely involved in the carcinogenesis. The aims of our study were to investigate the change of the members of LEF1/TCFs family in chronic inflammation associated colorectal carcinogenesis and the possible roles in carcinogenesis. Chronic inflammation-associated CRC was induced with the AOM-DSS mouse model. Gene expression array experiment was performed with the colonic tissue samples which were collected at different time points during the carcinogenesis. Data analysis strongly indicated that Wnt/β-catenin pathway was activated in chronic inflammation-related colorectal carcinogenesis. However, the members of LEF1/TCFs family showed different changes. The mRNA levels of LEF1 and TCF1 increased while the mRNA levels of TCF3 and TCF4 decreased with the formation of CRC, which were confirmed with real-time PCR. Although some of Wnt target genes were significantly up-regulated, such as MMP7 and Axin2, some were down-regulated, such as Nrcam. Most importantly, the members of LEF1/TCFs family showed the same expression profile in the human samples from normal colon, low grade adenoma, high grade adenoma and CRC. But the mRNA levels of the members were not correlated with the grade of CRC. Moreover, almost all of the target genes up-regulated in AOM-DSS model also increased in human CRC. Finally, prognosis analysis showed that up-regulation of LEF1, TCF1 and corresponding target genes were correlated with higher survival rate (p=0.0068). TCF3, TCF4 and the target genes down-regulated in AOM-DSS model were correlated with disease-free survival rate (p=0.03). Taken together, the members of LEF1/TCFs family changed differently in CRC independent of the status of inflammation. Members of LEF1/TCFs family combined with target genes may be potential prognostic biomarkers for CRC. Citation Format: Wenxiao Han, Bangrong Cao, Hongying Wang. Different change of LEF1/TCFs family members in colorectal carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1510. doi:10.1158/1538-7445.AM2013-1510