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Volume 131, Issue 2, Pages (August 2006)

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Presentation on theme: "Volume 131, Issue 2, Pages (August 2006)"— Presentation transcript:

1 Volume 131, Issue 2, Pages 630-639 (August 2006)
CD24 Is a New Oncogene, Early at the Multistep Process of Colorectal Cancer Carcinogenesis  Eyal Sagiv, Lorenzo Memeo, Adi Karin, Diana Kazanov, Jasmin Jacob–Hirsch, Mahesh Mansukhani, Gidi Rechavi, Hanina Hibshoosh, Nadir Arber  Gastroenterology  Volume 131, Issue 2, Pages (August 2006) DOI: /j.gastro Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

2 Figure 1 Microarray analysis to define differential gene expression, comparing (1) IEC-18 cells with (4) R1 cells and their derivatives under treatment with celecoxib. (3) IEC-18–resistant cells were held in 30 μmol/L celecoxib and (6) R1-resistant cells were held in 17 μmol/L celecoxib for around 6 months; both gained resistance by slowly increasing the drug dosages previously. The acute treatment of both (2) IEC-18 and (5) R1 cells included a single incubation of 72 hours in 20 μmol/L celecoxib. Normalized expression levels were calculated using Expander software. The vertical axis stands for the fold ratio of the expression of this cluster. The elevation of expression from IEC-18 to R1 cells and decrease in treated R1 cells should be noticed above all. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

3 Figure 2 Immunohistochemical staining for CD24 in colonic tissue. (A) Normal colonic mucosa (arrow) mostly shows no staining (the brown staining is a nonspecific endogenous peroxidase staining). (B) Colonic adenoma showing focally membranous luminal staining of neoplastic cells. (C) Colonic carcinoma shows more intensive staining in a membranous luminal distribution in the neoplastic epithelium than the adenoma (original magnification: A, 600×; B, 400×; C, 300×). Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

4 Figure 3 Anti-CD24 monoclonal antibodies selectively inhibit cell growth in human cancer cell lines that express CD24. (A) HT29, human colon cancer cells, show growth inhibition under treatment with SWA11, anti-CD24 monoclonal antibodies, developed in mouse ascitis fluid, in a time- and dose-dependent manner. The indicated dilutions of antibody in the medium were refreshed every 48 hours for 48 hours (green curve), 96 hours (pink curve), and 144 hours (yellow curve). (B) HT29 and Colo-357 (human colon and pancreatic cells, respectively) show a strong effect under treatment due to their high expression levels of CD24; SW480 and PANC1 (human colon and pancreatic cells, respectively) that express low levels of CD24 show a weak growth inhibition effect. Similar results were shown using 3 anti-CD24 monoclonal antibodies: SWA11, ML-5, and C-20. (C) HT29 cells were tested to their response to SWA11 anti-CD24 antibody in comparison with total immunoglobulins of preimmuned mice. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

5 Figure 4 Western blot analysis to CD24 protein levels in human cancer cell lines. Cell lysates (50 μg) from human CRC and pancreatic cancer cell lines were analyzed through 10% polyacrylamide gel electrophoresis for CD24 expression. Colo357 (lane 1) and Panc1 (lane 2) are human pancreatic cancer cells. Lane 3 is a control (no protein). HT29 (lane 4), SW480 (lane 5), HCT116 (lane 6), CaCo2 (lane 7), and Colo320 (lane 8) are human CRC cell lines. The blot was probed with mouse anti-CD24 (SWA11) antibodies and then with horseradish peroxidase–labeled anti-mouse antibodies. As a reference, cellular ubiquitous protein expression, β-actin, was analyzed. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions


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