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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 07, 2009 |
| Title |
Targetting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or siRNA |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
CD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogenactivated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer.
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| Overall design |
The study compared gene expression profiles between human CRC cells HT29 before and after expression of 1 and 2 shRNA vectors directed at the human CD24 gene, GFP control gene, HT29 cells and Colo357, human pancreatic cancer cells, before and after the inhibition of the CD24 molecule using 72h treatment with anti-CD24 monoclonal antibodies.
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| Contributor(s) |
Sagiv E, Starr A, Rozovski U, Khosravi R, Altevogt P, Wang T, Arber N |
| Citation(s) |
18413748 |
| Submission date |
Mar 04, 2009 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Eyal Sagiv |
| E-mail(s) |
sagiveyal@yahoo.com
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| Organization name |
Tel Aviv Medical Center
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| Department |
The Integrated Cancer Prevention Center
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| Lab |
Laboratory for Cell and Molecular Biology
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| Street address |
6th Weizmann st
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| City |
Tel Aviv |
| ZIP/Postal code |
64253 |
| Country |
Israel |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA114851 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE15102_RAW.tar |
17.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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