colorectal hyperplasia and dysplasia due to human carcinoembryonic antigen (cea) family member expression in transgenic mice结直肠增生和发育不良由于人类癌胚抗原(cea)家庭成员表达转基因小鼠.pdf

Colorectal Hyperplasia and Dysplasia Due to Human Carcinoembryonic Antigen (CEA) Family Member Expression in Transgenic Mice Carlos H. F. Chan.*, Pilar Camacho-Leal., Clifford P. Stanners* ´ ´ McGill Cancer Centre, Department of Biochemistry, McGill University, Montreal, Quebec, Canada CEA and CEACAM6 are immunoglobulin family intercellular adhesion molecules that are up-regulated without structural mutations in approximately 70% of human cancers. Results in in vitro systems showing tumorigenic effects for these molecules suggest that this correlation could indicate an instrumental role in tumorigenesis. To test whether this applies in vivo, transgenic mice harboring 187 kb of the human genome containing four CEA family member genes including the CEA and CEACAM6 genes were created and their copy numbers increased by mating until colonocyte expression levels reached levels seen in human colorectal carcinomas. The colonocyte surface level of integrin a5 and the activation of AKT increased progressively with the expression levels of CEA/CEACAM6. Colonic crypts showed a progressive increase in colonocyte proliferation, an increase in crypt fission, and a strong inhibition of both differentiation and anoikis/apoptosis. All transgenic mice showed massively enlarged colons comprising a continuous mosaic of severe hyperplasia, dysplasia and serrated adenomatous morphology. These results suggest that up-regulated non-mutated adhesion molecules could have a significant instrumental role in human cancer. Citation: Chan CHF, Camacho-Leal P, Stanners CP (2007) Colorectal Hyperplasia and Dysplasia Due to Human Carcinoembryonic Antigen (CEA) Family Member Expression in Transgenic Mice. PLoS ONE 2(12): e1353. doi:10.