Novel Gene Ic53 Promote Colon Cancer Development And Its Molecular Mechanism

IC53 is a novel gene cloned from human aorta cDNA library. Computational analysis showed that IC53 cDNA is 2538 bp long, encoding 419 amino acids, mapped to chromosome 17q21.31, IC53 cDNA has an insert sequence of 708bp (357-1064) compared with that of human C53. Comparison analysis of IC53 indicates that IC53 has 84% of identity to mouse C53. IC53 was expressed in various tissues including brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung, peripheral blood leukocytes, and tumor cell lines such as Promyelocytic Leukemia HL-60, Chronic Myelogenous Leukemia K-562, Lymphoblastic Leukemia MOLT-4, Burkitt's Lymphoma Raji, Colorectal Adenocarcinoma SW480, Lung Carcinoma A549, Melanoma G-361. Two transcripts of 2.0 and 3.2 kilobase pairs (kb) were identified in all the normal tissues and the 3.2kb transcript was selectively highly expressed in the peripheral blood leukocytes, liver and kidney, whereas the 2.0 kb transcript in heart. These two transcripts were also present in all tested tumor cell lines with the highest expression in Promyelocytic Leukemia HL-60, Lymphoblastic Leukemia MOLT-4, and Burkitt's Lymphoma Raji.Our previous study demonstrated that IC53 gene was overexpressed in colon cancer. We compared the expression level of IC53 between 12 cancer tissues including breast cancer, uterus cancer, colon cancer, stomach cancer, ovary cancer, lung cancer, kidney cancer, rectum cancer, thyroid cancer, cervix cancer, prostate cancer, pancreas cancer, small intestine cancer and their corresponding controls by Cancer Profiling Array from Clontech and found that IC53 was upregulated in colon cancer, further confirmed by immunohistochemistry and in situ hybridization.To explore the role of IC53 in colon cancer progression, we employed a set of colon cancer cells (HCT-116 cell lines and HT29 cell lines) that were stably transfected with empty vectors and IC53. Cell proliferation, adhesion and migration play a key role in cancer progression, and we found that stable transfection of IC53 stimulated HCT-116 and HT29 cell proliferation by MTT assay and HCT-116 and HT 29 migration by using transwell analysis respectively. Overexpression of IC53 gene also increased cell adhesion of HCT-116 cells. All these rusults were further confirmed by RNAi methods. Tumorigenesis assay indicated that stable transfection of IC53 can increase HCT-116 cells tumorigenic ability in nude mice. All these results above indicated that IC53 could promote colon cancer progression.