The nuclear to cytoplasmic shift of ING5 protein during colorectal carcinogenesis with their distinct links to pathologic behaviors of carcinomas

• Published in: Human pathology 2011-03, Vol.42 (3), p.424-433
• Main Authors: Zheng, Hua-chuan, MD, PhD, Xia, Pu, MD, Xu, Xiao-yan, PhD, Takahashi, Hiroyuki, MD, PhD, Takano, Yasuo, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adenoma - genetics; Adenoma - metabolism; Adenoma - pathology; Aged; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cell Nucleus - metabolism; Cell Nucleus - pathology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cytoplasm - metabolism; Cytoplasm - pathology; Female; Fluorescent Antibody Technique, Direct; Gastroenterology. Liver. Pancreas. Abdomen; Humans; ING5; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Pathogenesis; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Progression; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tissue Array Analysis; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2009.12.018

Summary 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.