CD74 is a survival receptor on colon epithelial cells.
OBJECTIVE
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.


CONCLUSIONS
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.
Maharshak
Nitsan
N
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Cohen
Sivan
S
Lantner
Frida
F
Hart
Gili
G
Leng
Lin
L
Bucala
Richard
R
Shachar
Idit
I
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism*; D066298:In Vitro Techniques; D008263:Macrophage Migration-Inhibitory Factors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D000944:Antigens, Differentiation, B-Lymphocyte; D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C045084:invariant chain; D051057:Proto-Oncogene Proteins c-akt