Study On Molecular Mechanisms Of ESCC Deregulated Gene Fibronectin, TGase 3 In Tumorigenesis And Embryogenesis

Esophageal cancer is one of the ten most frequent malignant tumors in the world. It ranks the forth in the mortality of tumors in our country, and about 40% cases of esophageal cancer is occurred in China. It exists in 2 main histopathological types-esophageal squamous cell caicinoma (ESCC) and esophageal adenocarcinoma (EADC). In China, about 90% of esophageal cancers are ESCCs. Due to the relatively late stage of diagnosis and poor treatment, five-year survival rate remains below 10%. The development of better treatment modalities and better therapeutic and preventive approaches requires the understanding of the molecular mechanisms of the complex process of esophageal tumorigenesis.The development of esophageal cancer is a complex multi-step process, involving various genetic change and various factors. Previous studies indicated that the tumorgenesis of esophageal is the result from the interact of environmental risk factors and genetic factors。Previous work in our lab has shown that a Mendelian autosomal recessive major gene may contribute to the genetics susceptibility to ESCC。Therefore, to seek the ESCC-related genes and study the function of them is very important for elucidating the molecular mechanisms of esophageal carcinogenesis.1 Expression patterns of esophageal cancer deregulated genes in C57BL/6J mouse embryogenesisTo explore the function of esophageal cancer related genes, the expression patterns of 90 ESCC deregulated genes (66 known genes and 24 novel) in mid to late stages of C57BL/6J mouse embryogenesis (embryonic d 11.5, d 13.5, and postnatal d1) were analyzed using reverse northern screening. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to confirm some of the result.By reverse northern screening, the comparison results showed that the expression patterns of these genes were diverse and complex. Four patterns of expression were seen at the three stages of E11.5, E13.5 and P1: (1) up-regulation during the E11.5 period, down at E13.5 and P1 (up-down-down), the 10 up-regulated genes could be classed into 6 known genes and 4 unknown genes. The known genes include differentiation related genes (S100A8), immunity related gene (IGL), translation and transcription regulation genes (RPL15, EEF1A1), cytoskeleton protein (TUBA1), cysteine protease inhibitor (cystatin B);(2) up-regulation during the E13.5 and postnatal 1 day period (down-up-up), such as the SPRR2A which was down-regulated at E11.5; (3) down-regulation during the E11.5 and E13.5 period and up regulated at postnatal 1 day (down-down-up), such as RHCG and keratin 4; (4) fluctuating expression, down initially, up at E13.5, and then down again (down-up-down), such as EMP1,which was highly expressed at E13.5.In summary, mouse embryo provides an important model system for studying the gene function. Esophageal cancer deregulated genes showed several kinds of expression pattern during embryogenesis. The different expression genes in embryogenesis covered a broad spectrum of biologic functions including cell proliferation, differentiation, immune response, cytoskeleton protein, migration, etc. Our study suggests that S100A8 and S100A9 may play different roles in early embryonic development, IGL may be an oncofetal protein, and EMP1 relates with neurogenesis at E13.5. Our results will be helpful for understanding the function of the ESCC deregulated genes in embryonic development and tumorigenesis. The genes identified pertinent to embryonic development may serve as candidate susceptibility genes for esophageal cancer disorders as well as for various disorders of embryonic development. 2 Temporal and spatial expression of differentiation-associated gene transglutaminase 3 in C57BL/6J mouse embryogenesisTransglutaminase 3(TGase 3) is a predominantly member of transgutaminase family that have been implicated in the formation of the cornified envelope (CE). CE serves as a vital barrier function involved in the skin formation, the defection of CE formation may play important ro...