title: The nuclear to cytoplasmic shift of ING5 protein during colorectal carcinogenesis with their distinct links to pathologic behaviors of carcinomas.
abstract: Inhibitor of growth 5, a tumor suppressor protein, can interact with p53, thereby inhibiting cell growth and inducing apoptosis. Inhibitor of growth 5 overexpression results in a reduction in colony-forming efficiency and cell population in S phase. To clarify the roles of inhibitor of growth 5 in tumorigenesis and progression of colorectal carcinomas, we examined inhibitor of growth 5 expression by immunohistochemistry on a tissue microarray containing colorectal carcinomas (n = 306), adenomas (n = 69), and nonneoplastic mucosa (n = 288) and compared this with clinicopathologic parameters of the carcinomas. In addition, inhibitor of growth 5 expression in colorectal carcinoma tissues and cell lines (DLD-1, HCT-15, SW480, and WiDr) was analyzed by Western blot and reverse transcriptase-polymerase chain reaction. It was found that the inhibitor of growth 5 protein was localized to the nuclei of colon carcinoma cells with no differences at mRNA levels. Among 18 frozen samples of colorectal carcinoma, significantly increased expression of inhibitor of growth 5 protein was observed in the carcinoma in comparison with adjacent mucosa in 14 cases (77.8%; P < .05), and 71.4% (10/14) of carcinoma cases exhibited up-regulated inhibitor of growth 5 mRNA expression. Decreased inhibitor of growth 5 expression was detected by immunohistochemistry in colorectal carcinoma, compared with non-neoplastic mucosa and adenoma (P < .05). Nuclear inhibitor of growth 5 expression was negatively correlated with tumor size, depth of invasion, degree of dedifferentiation, and Union Internationale Contre le Cancer staging (P < .05). In contrast, cytoplasmic inhibitor of growth 5 expression was positively correlated with depth of invasion, lymphatic invasion, and Union Internationale Contre le Cancer staging (P < .05). It was suggested that aberrant inhibitor of growth 5 expression may contribute to pathogenesis, growth, and invasion of colorectal carcinomas and could be considered as a promising marker to gauge aggressiveness of colorectal carcinomas.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110001, China. zheng_huachuan@hotmail.com
authors.forename: Hua-chuan
authors.initials: HC
authors.lastname: Zheng
authors.forename: Pu
authors.initials: P
authors.lastname: Xia
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Xu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C508131:ING5 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins