Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Coppola
Domenico
D
Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, Florida 33612-9497, USA. Domenico.Coppola@moffitt.org
Khalil
Farah
F
Eschrich
Steven A
SA
Boulware
David
D
Yeatman
Timothy
T
Wang
Hong-Gang
HG
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D046888:Tissue Array Analysis
D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; C429293:SH3GLB1 protein, human