The DCC gene product in cellular differentiation and colorectal tumorigenesis.
The analysis of human colorectal tumors has revealed frequent loss of heterozygosity (LOH) of the long arm of chromosome 18. A novel gene, DCC (deleted in colorectal cancer), located within the region of LOH on chromosome 18q was identified and has been implicated as a tumor suppressor gene. We have now shown that DCC encodes a membrane-bound protein of the immunoglobulin-CAM family, as demonstrated by cell-surface labeling, immunohistochemical analysis, and sequencing of cDNA clones. The DCC protein was found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Colorectal tumors that lost their capacity to differentiate into mucus producing cells uniformly lacked DCC expression and loss of a chromosome 18q allele was often accompanied by loss of DCC expression in colon tumors. These results provide evidence that DCC encodes a cell surface-localized protein and emphasize the inverse relationship between differentiation and tumorigenesis.
Hedrick
L
L
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Cho
K R
KR
Fearon
E R
ER
Wu
T C
TC
Kinzler
K W
KW
Vogelstein
B
B
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D018256:Adenomatous Polyps / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000075389:DCC Receptor; D018076:DNA, Complementary; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC; D006801:Humans; D007417:Intestinal Polyps / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D018076:DNA, Complementary; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins