Expression And Function Of Forkhead Box E1in Colorectal Cancer

Forkhead box El (FOXE1), also known as thyroid transcripition factor2(TTF-2), belongs to a large family of forkhead transcripition factors. It is located on chromosome9q22, and plays important roles in embryogenesis, cell growth and differentiation. Rencent studies also point to a relevant association of FOXE1with some types of cancers. FOXE1is considered to be a susceptibility gene of thyroid papillary carcinoma, and cancer-specific FOXE1hypermethylation events were found in patients with pancreatic cancer, breast cancer, cutaneous squamous cell cancer as well as colorectal cancer. However, the expression and function of FOXE1in tumorigenesis of colorectal cancer is still unkown.Purpose:We will investigate the expression and the expression control mechanisms of FOXE1gene in colorectal cancer. And study its biological role in carcinogenesis and progression of colorectal cancer.Method:The expression of FOXE1in colorectal cancer cell lines and colorectal cancer tissues were assessed by Semi-Quantitative RT-PCR and immunohistochemistry. Compare the level of FOXE1promoter methylation by methylation-specific PCR (MSP) and bisulfite genome sequencing (BGS). Subsequently, we establish stable FOXE1expression colon cancer cell line to observe its biological effect on colorectal cancer, including cell growth, cell cycle, migration, cell apoptosis, actin cytoskeleton and the growth of human colorectal DLD1xenograft in nude mice.Result:We found that the expression of FOXE1is silenced or down-regulated in the majority of colorectal cancer cell lines and cancer tissues. Hypermethylation of CpG islands in the promoter region of FOXE1was detected in almost all the colorectal tumors, but not in normal colon mucosal tissues. FOXE1was highly expressed in normal colon mucosal tissues, while its expression exhibited low to undetectable levels in colorectal cancer tissues. The high expression rates of FOXE1protein in primary colorectal cancer tissues and metastatic lymph nodes were only25%(32/128) and7.4%(2/27), respectively. Low FOXE1expression was significantly correlated with lymph node metastatsis and advanced TNM stages. Ectopic expression of FOXE1could suppress tumor cell growth and migration and affect the organization of actin cytoskeleton as well as suppress the tumorigenicity in vivo.Conclusion:FOXE1methylation was frequently seen in association with a complete absence of or downregulated gene expression in colorectal cancer and FOXE1plays a suppressive role in the development and progression of colorectal cancer.