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- Title
Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma.
- Authors
Coppola, Domenico; Khalil, Farah; Eschrich, Steven A.; Boulware, David; Yeatman, Timothy; Hong-Gang Wang; Wang, Hong-Gang
- Abstract
<bold>Background: </bold>Bax-interacting factor-1 (Bif-1) protein is a member of the endophilin B family that plays a critical role in apoptosis, autophagy, and mitochondrial morphology. Loss of Bif-1 suppresses programmed cell death and promotes tumorigenesis. The connection of Bif-1 to colorectal cancer remains to be evaluated.<bold>Methods: </bold>To determine Bif-1 expression in human colorectal adenocarcinoma (CRC), the authors performed immunohistochemistry using stage-oriented cancer tissue microarrays containing 102 CRC samples of different stages and 38 samples of normal colorectal mucosa (NR). Formalin-fixed, paraffin-embedded core sections on the tissue array were immunostained using the avidin-biotin-peroxidase method and the anti-Bif-1 murine monoclonal antibody. Bif-1 staining was scored by 2 independent observers. To examine Bif-1 mRNA levels, the authors performed DNA microarray analysis of 205 CRC and 10 NR samples.<bold>Results: </bold>Bif-1 expression was negative in 22.5% (23 of 102) of CRCs. Moderate to strong Bif-1 staining was identified in 36.3% (37 of 102) of the tumors, and weak staining was noted in 41.2% (42 of 102). Twenty-six of 38 (68.4%) NR samples exhibited moderate to strong Bif-1 immunoreactivity, and none of them was negative. In 12 (31.6%) cases NR demonstrated weak Bif-1 stain. The mean (median) scores for CRCs and NR differed significantly: 3.2 (3.0) and 5.2 (6.0), respectively (P = .0003). The percentage of cases with negative expression also differed significantly between NR and CRC (P = .002). Decreased Bif-1 expression in CRCs was confirmed at the mRNA level by microarray analysis.<bold>Conclusions: </bold>The authors report the down-regulation of Bif-1 during the transition from NR to CRC, a novel finding in agreement with the tumor suppressor function of Bif-1.
- Subjects
UNITED States; TUMOR suppressor proteins; ADENOCARCINOMA; COLON cancer; CELL morphology; IMMUNOCHEMISTRY; RNA analysis; BIOCHEMISTRY; CARRIER proteins; COLON tumors; COMPARATIVE studies; IMMUNOHISTOCHEMISTRY; PHENOMENOLOGY; RESEARCH methodology; MEDICAL cooperation; RECTUM tumors; RESEARCH; EVALUATION research; OLIGONUCLEOTIDE arrays; TISSUE arrays; GENE expression profiling
- Publication
Cancer (0008543X), 2008, Vol 113, Issue 10, p2665
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.23892