Deficiency of Interferon-Gamma or Its Receptor Promotes Colorectal Cancer Development

摘要: Genetic variations in interferon-gamma (IFN-γ) and its receptor (IFNγR) subunits are closely associated with the risk of colorectal cancer (CRC) survival after diagnosis. However, role loss IFN-γ or IFNγR function pathogenesis CRC remains unclear. Here, we investigated endogenous deficiency adenomatous polyposis coli (Apc)-mediated intestinal tumor by developing a variant Apc(Min/+) mice. The Apc(Min/+)IFN-γ(+/-) mice presented increased number size adenomas, 41.7% these developed adenocarcinoma. Molecular analyses adenomas suggested that heterozygous deletion promoted EGFR/Erk1/2 Wnt/β-catenin signaling. In vitro, administration inhibited Apc-mutated HT-29 colon cell proliferation had no effect on HCT-116 cells express wild-type Apc. Besides, challenged small interfering RNA targeting one IFNγR1. We found knockdown IFNγR1 stimulated colony formation, which was also related to regulation Thus, our results strongly support notion act as rate-limiting factor development CRC, uncovering novel for them biology.