Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome driven by germline loss-of-function of the APC gene and phenotypically manifests with intestinal polyposis and a variety of extra-intestinal bone and soft tissue tumors.
Familial adenomatous polyposis (FAP) is an autosomal dominant form of intestinal polyposis and colorectal cancer caused by germ-line mutations in the adenomatous polyposis coli (APC) gene.
Mutations in APC are classically associated with familial adenomatous polyposis (FAP), a highly penetrant autosomal dominant disorder characterized by multiple intestinal polyps and, without surgical intervention, the development of colorectal cancer (CRC).
Here we show that conditional inactivation of Bmpr1a in mice disturbs homeostasis of intestinal epithelial regeneration with an expansion of the stem and progenitor cell populations, eventually leading to intestinal polyposis resembling human juvenile polyposis syndrome.
A recent study showed that Cdx2 null mutation was embryonically lethal, whereas Cdx2+/- mice developed multiple intestinal polyps in the proximal colon in addition to developmental defects.
Because of the implication of Plzf in the regulation of stem cell maintenance, as well as Wnt and Ras signaling, in other systems, our observations suggest that the novel genetic relationship between CUX1 and PLZF could be of relevance to human diseases, such as leukemia, and open up a new field of investigation for the implication of these regulators during intestinal polyposis and cancer.
Moreover, a single copy (heterozygote) deletion of CXCR2 gene was sufficient to synergize with a low-dose sulindac treatment in suppressing APCmin-induced intestinal polyposis.