Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jul 14, 2010; 16(26): 3258-3266
Published online Jul 14, 2010. doi: 10.3748/wjg.v16.i26.3258
CD74 is a survival receptor on colon epithelial cells
Nitsan Maharshak, Sivan Cohen, Frida Lantner, Gili Hart, Lin Leng, Richard Bucala, Idit Shachar
Nitsan Maharshak, Sivan Cohen, Frida Lantner, Gili Hart, Idit Shachar, Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel
Nitsan Maharshak, Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Lin Leng, Richard Bucala, Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, United States
Author contributions: Maharshak N and Cohen S contributed equally to this article; Maharshak N, Cohen S, Lantner F, Hart G and Shachar I designed the research; Maharshak N, Cohen S, Lantner F and Hart G performed the research; Maharshak N, Cohen S and Shachar I analyzed the data; Leng L and Bucala R contributed essential reagents; Maharshak N, Cohen S, Bucala R and Shachar I wrote the paper.
Supported by The Israel Science Foundation (Morasha), the Minerva foundation, the Israel Cancer Association, and the Moross institute
Correspondence to: Idit Shachar, PhD, Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. idit.shachar@weizmann.ac.il
Telephone: +972-8-9344257 Fax: +972-8-9344141
Received: November 10, 2009
Revised: January 24, 2010
Accepted: January 31, 2010
Published online: July 14, 2010
Abstract

AIM: To investigate the expression and function of CD74 in normal murine colon epithelial cells (CEC) and colon carcinoma cells.

METHODS: Expression of CD74 mRNA and protein were measured by reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and fluorescence-activated cell sorter (FACS). The effect of migration inhibitory factor (MIF) on the survival of normal CEC from C57BL/6, NOD/SCID, and CD74 deficient mice both in vitro and in vivo, and on the CT26 carcinoma cell line was analyzed by (quantitative) qRT-PCR, RT-PCR, Western blotting and FACS.

RESULTS: CD74 was found to be expressed on normal CEC. Stimulation of CD74 by MIF induced a signaling cascade leading to up-regulation of Bcl-2 expression, resulting in a significant increased survival of CEC. CD74 was also expressed on the CT26 colon carcinoma cell line and its stimulation by MIF resulted in enhanced cell survival, up-regulation of Akt phosphorylation and Bcl-2 expression.

CONCLUSION: CD74 is expressed on CEC and colon carcinoma cells and serves as a survival receptor in these cells. These results may have implications on colorectal cancer research.

Keywords: CD74, Migration inhibitory factor, Colon epithelial cells