title: Lentivirus-mediated somatic recombination and development of a novel mouse model for sporadic colorectal cancer.
abstract: In this study, we have developed a novel mouse model for sporadic colorectal cancer (CRC) by utilizing APC conditional knockout (Apc(CKO) ) mouse and lentivirus encoding Cre recombinase and a reporter gene (EGFP or LacZ). Lentiviral transduction of colonic crypt stem cells allowed for the long-term expression of reporter gene as well as excision of floxed Apc alleles, which resulted in tumor development. Tumors represented adenoma stages along with the nuclear accumulation of β-catenin. Loss of E-cadherin at the cellular junctions and strong expression of Vimentin suggested the sign of active epithelial-mesenchymal transition. Moreover, nuclear staining of Ki67 inside epithelial cells of aberrant crypts demonstrated their higher proliferative nature. Erratic downstream signaling of activated Wnt/β-catenin, AKT/mTOR, and Notch pathways provided strong evidence towards the higher proliferative index of epithelial cells inside the aberrant crypts. These results do recapitulate the findings of previous APC mutant mouse models. Our model represents sporadic CRC more precisely as (i) tumors result from somatic mutations but not from germline; (ii) tumors develop in colon not in small intestine; (iii) few tumors develop at the distal end of colons. Additionally, our model allows for the long-term expression of the gene(s), which get integrated into the host cell genome and provides an ability to track the tumor growth. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biological Sciences, Center for Colon Cancer Research, University of South Carolina, Columbia, SC, 29208.
authors.forename: Vivek
authors.initials: V
authors.lastname: Vaish
authors.affiliation: Department of Biological Sciences, Center for Colon Cancer Research, University of South Carolina, Columbia, SC, 29208.
authors.forename: Joohwee
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Center for Colon Cancer Research, University of South Carolina, Columbia, SC, 29208.
authors.forename: Minsub
authors.initials: M
authors.lastname: Shim
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011995:Recombination, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D012333:RNA, Messenger; D051176:beta Catenin