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Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma
Article first published online: 2 OCT 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 10, pages 2665–2670, 15 November 2008
How to Cite
Coppola, D., Khalil, F., Eschrich, S. A., Boulware, D., Yeatman, T. and Wang, H.-G. (2008), Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma. Cancer, 113: 2665–2670. doi: 10.1002/cncr.23892
- Issue published online: 3 NOV 2008
- Article first published online: 2 OCT 2008
- Manuscript Accepted: 25 JUN 2008
- Manuscript Revised: 11 JUN 2008
- Manuscript Received: 20 MAR 2008
- American Cancer Society. Grant Number: RSG-05-244-01-CCG
- National Institutes of Health. Grant Number: CA82197
- colon adenocarcinoma;
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.
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.
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.
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. Cancer 2008. © 2008 American Cancer Society.