CD24 is a new oncogene, early at the multistep process of colorectal cancer carcinogenesis.
OBJECTIVE
The aim of this study was to identify genes that play a role in colorectal cancer (CRC) carcinogenesis by analysis of differential gene expression of normal and transformed CRC cell lines.


METHODS
Gene expression array analysis ([RG-U34] GeneChip) was performed in normal and transformed rat intestinal epithelial cells before and after exposures to celecoxib. In particular, we were looking for (1) altered gene expression in the transformed cells that reverts to normal following exposure to a selective cyclooxygenase-2 inhibitor, (2) novel genes, and (3) genes encoding membrane receptors or ligands. As a validation of the results and for human patients, immunohistochemistry was performed on 398 biological samples from the gastrointestinal tract (normal, polyps, and adenocarcinomas). Human cancer cell lines were tested for their response to anti-CD24 monoclonal antibodies.


RESULTS
A total of 1081 genes were differently expressed following malignant transformation; 71 genes showed altered expression that reverted to normal following treatment with celecoxib, including the CD24 gene. Immunohistochemistry confirmed that increased expression of CD24 is an early event in CRC carcinogenesis. It was expressed in 90.7% of adenomas and 86.3% of CRCs. Very low expression was seen in normal epithelium (16.6%). Human cancer cell lines showed growth inhibition in response to the antibodies, according to their expression levels of CD24 and in dose- and time-dependent manners. These results were repetitive for 3 different antibodies.


CONCLUSIONS
CD24 is overexpressed in the colonic mucosa, already at an early stage of carcinogenesis. It may be a useful target for early detection and in CRC therapy.
Sagiv
Eyal
E
Department of Cancer Prevention, Tel Aviv Medical Center, Tel Aviv, Israel.
Memeo
Lorenzo
L
Karin
Adi
A
Kazanov
Diana
D
Jacob-Hirsch
Jasmin
J
Mansukhani
Mahesh
M
Rechavi
Gidi
G
Hibshoosh
Hanina
H
Arber
Nadir
N
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D051927:CD24 Antigen / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D051381:Rats
D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; D012334:RNA, Neoplasm