Interplay between APC and ALDH1B1 in a newly developed mouse model of colorectal cancer.

BACKGROUND

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Mutations in the adenomatous polyposis coli (APC) gene are pivotal in colorectal tumorigenesis. Recently, we demonstrated that aldehyde dehydrogenase 1B1 (ALDH1B1) knockdown dramatically reduced colon tumor growth in a mouse xenograft model. The purpose of the present preliminary study is to examine the effect of loss of ALDH1B1 in CRC development in an inducible colon-specific Apc mouse model.

METHODS

ApcCdx2 mice develop uni-allelic inactivation of Apc specifically in colon epithelial cells following tamoxifen treatment. Aldh1b1 KO mice were crossed with ApcCdx2 mice. Six-month-old male ApcCdx2/Aldh1b1, and ApcCdx2/Aldh1b1 mice were treated with tamoxifen (50 mg/kg, i.p.) for three consecutive days. Apc/Aldh1b1 and Apc/Aldh1b1 mice were treated with corn oil (i.e., tamoxifen vehicle control) for three consecutive days. Eighteen days later, mice were sacrificed and their colons examined microscopically, macroscopically and histologically for the presence of adenoma.

RESULTS

All ApcCdx2/Aldh1b1 and ApcCdx2/Aldh1b1 mice treated with tamoxifen developed colorectal adenoma. The ApcCdx2/Aldh1b1 mice showed a significant decrease in the total volume of all ileal and colonic adenomas, and decreased incidence of large colonic adenoma compared to ApcCdx2/Aldh1b1 mice. Immunohistochemical analysis of p53 and β-catenin showed a trend toward decreased expression score in colonic adenomas of ApcCdx2/Aldh1b1 mice.

CONCLUSION

The present preliminary study suggests that deletion of ALDH1B1 may protect against the full development of colorectal cancer. Further mechanistic studies are required to elucidate how ALDH1B1 contributes for colorectal cancer.