Tissue and cell-specific patterns of expression of rat liver and intestinal fatty acid binding protein during development and in experimental colonic and small intestinal adenocarcinomas.
BACKGROUND
Mammalian small intestinal and colonic epithelium express members of a multigene family of hydrophobic ligand binding proteins of which liver and intestinal fatty acid binding protein represent among the most abundant intestinal gene products. These proteins are expressed in a cell- and region-specific manner and emerge in a temporally distinctive pattern.


METHODS
We have studied expression of these genes in the small intestine and colon of rats treated with 1,2-dimethylhydrazine since these animals develop a predictable pattern of both small and large bowel cancers. Studies were also undertaken in fetal and neonatal small intestine and colon.


RESULTS
There was a 10- and 50-fold decrease, respectively, in mRNA abundance for intestinal and liver fatty acid binding protein in RNA from colon cancers compared with either uninvolved or control RNA. Immunocytochemical analysis revealed decreased staining for both proteins within their normal distribution together with ectopic clusters of cells reactive for liver fatty acid binding protein within colonic tumors. A more striking mosaic of immunocytochemical staining for both liver and intestinal fatty acid binding protein was found in small intestinal adenocarcinomas. Similar mosaic patterns of immunocytochemical staining were transiently detectable in rat fetal small intestine and neonatal colon.


CONCLUSIONS
The region- and cell-specific expression of these genes, which may be linked temporally to events in intestinal differentiation, are subject to disruption in a cell-specific manner in the transformed, or dedifferentiated, phenotype.
Davidson
N O
NO
Department of Medicine, University of Chicago, Illinois.
Ifkovits
C A
CA
Skarosi
S F
SF
Hausman
A M
AM
Llor
X
X
Sitrin
M D
MD
Montag
A
A
Brasitus
T A
TA
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced / Q000737:chemistry*; D000818:Animals; D002273:Carcinogens; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D003106:Colon / Q000737:chemistry* / Q000196:embryology / Q000254:growth & development; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000737:chemistry*; D004127:Dimethylhydrazines; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000737:chemistry*; D007421:Intestine, Small / Q000737:chemistry* / Q000196:embryology / Q000254:growth & development; D008297:Male; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins
D002273:Carcinogens; D002352:Carrier Proteins; D004127:Dimethylhydrazines; C107608:FABP7 protein, human; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D019813:1,2-Dimethylhydrazine