title: CD24 knockout prevents colorectal cancer in chemically induced colon carcinogenesis and in APC(Min)/CD24 double knockout transgenic mice.
abstract: Increased expression of CD24 is seen in a large variety of solid tumors, including up to 90% of gastrointestinal (GI) tumors. Stable derivatives of SW480 colorectal cancer (CRC) cells that overexpress CD24 proliferate faster, and increase cell motility, saturation density, plating efficiency, and growth in soft agar. They also produce larger tumors in nude mice as compared to the parental SW480 cells. Most significantly, even depletion of one copy of the CD24 allele in the APC(Min/+) mice of a transgenic mouse model led to a dramatic reduction in tumor burden in all sections of the small intestine. Homozygous deletion of both CD24 alleles resulted in complete abolishment of tumor formation. Moreover, CD24 knockout mice exhibited resistance to chemically induced inflammation-associated CRC. Finally, a new signal transduction pathway is suggested: namely, CD24 expression downstream to COX2 and PGE2 synthesis, which is directly regulated by β-catenin. CD24 is shown in vitro and in vivo as being an important oncogene in the gut, and one that plays a critical role in the initiation and progression of carcinogenesis.
authors: The Integrated Cancer Prevention Center Tel Aviv Sourasky Medical Center Tel Aviv Israel Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Inna
authors: I
authors: Naumov
authors: Alona
authors: A
authors: Zilberberg
authors: Shiran
authors: S
authors: Shapira
authors: Doran
authors: D
authors: Avivi
authors: Dina
authors: D
authors: Kazanov
authors: Rina
authors: R
authors: Rosin-Arbesfeld
authors: Nadir
authors: N
authors: Arber
authors: Sarah
authors: S
authors: Kraus
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D001397:Azoxymethane / Q000494:pharmacology; D051927:CD24 Antigen / Q000096:biosynthesis / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics; D016264:Dextran Sulfate / Q000494:pharmacology; D015232:Dinoprostone; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007421:Intestine, Small; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000235:genetics; D047368:Tumor Burden / Q000235:genetics; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D051176:beta Catenin; D016264:Dextran Sulfate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D001397:Azoxymethane
keywords: ApcMin; CD24; knockout mice; oncogene; β-catenin