title: Immunohistochemical and mutational analysis of apoptosis-inducing factor (AIF) in colorectal carcinomas.
abstract: Apoptosis-inducing factor (AIF) has a principal role in caspase-independent apoptosis. In addition, AIF has a vital oxidoreductase activity that is required for cell survival. It may be important to identify the alterations of the AIF gene and AIF protein expression to see the function of AIF in human cancers. In this study we analyzed the expression of AIF protein in 103 colorectal carcinomas by immunohistochemistry. We also analyzed the mutation in exons 10-15 of AIF encoding the region that possesses the cell death function of AIF by single-strand conformation polymorphism (SSCP) in 48 colorectal, 48 gastric, 48 breast and 48 hepatocellular carcinomas, and 48 leukemias. By immunohistochemistry, AIF protein expression was detected in both cancer cells and normal mucosal epithelial cells in all of the 103 colorectal carcinoma tissues. However, the cancer cells showed higher intensities of AIF immunostaining than the normal cells in 83 cases (80.5%). AIF immunoreactivities were observed in the cancers irrespective of their location or the depth of invasion. Mutational analysis detected one AIF mutation in the colorectal carcinomas, but none in the other cancers. The AIF mutation detected was a two-base deletion mutation in intron 15. The increased expression of AIF in the malignant colorectal epithelial cells compared to the normal mucosal epithelial cells suggests that AIF expression may play a role in colorectal tumorigenesis. The data also suggest that somatic mutation of AIF is a rare event in common human cancers.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Socho-Gu, Seoul, Korea.
authors.forename: Eun Goo
authors.initials: EG
authors.lastname: Jeong
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Soung
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D004273:DNA, Neoplasm