Role of Reduced Bdnf Expression in Novel Apc Mutant Allele-induced Intestinal and Colonic Tumorigenesis in Mice.

ABSTRACT

BACKGROUND/AIM: Brain-derived neurotrophic factor (BDNF) is a growth factor of the neurotrophin family. Recent studies indicate that its expression is regulated by Wnt/ß-catenin signaling. In this study, we aimed to examine the effects of reduced Bdnf levels in an Apc mutant intestinal/colonic tumor mouse model. MATERIALS AND METHODS: We crossed Apc+/- and Bdnf+/- C57BL/6 mice. After genotyping the litters, Apc+/+ Bdnf+/+ (wild-type, wt), Apc+/- Bdnf+/+ (Apc mutant), Apc+/+ Bdnf+/- (Bdnf mutant), and Apc+/- Bdnf+/- (Apc/Bdnf double mutant) mice cohorts were generated. All mice were followed daily for 36 weeks and weighed once a week, and mice that died or reached a terminal stage before this period were also recorded and dissected. At the end of this period, all surviving mice were sacrificed, and tissue samples were collected. Polyp numbers in the small intestine and colon were counted. Microscopic slides were prepared for histopathological examination. Protein extraction was performed both for tumor and normal tissue analysis. RESULTS: A significant weight gain was observed in the Bdnf mutant and Apc/Bdnf double mutant cohorts compared to wt and Apc mutant controls. In Apc/Bdnf double mutant mice, the small intestinal polyp count was slightly decreased, and the colon polyp count increased significantly, and developed the disease phenotype significantly later than Apc mutant mice. CONCLUSION: Bdnf level has an important role in the Apc mutant intestinal and colonic tumorigenesis model. Modulation of Bdnf levels can be a potential therapeutic target in colorectal cancer.