Identification of candidate genes in ulcerative colitis and Crohn's disease using cDNA array technology.
Inflammatory bowel disease (IBD) follows a multigenic mode of inheritance, encompassing the clinically discrete phenotypes of ulcerative colitis (UC) and Crohn's disease (CD). The risk of malignant transformation of the colon increases with the duration and extent of IBD and is particularly high for patients with a longstanding history of UC. We wished to identify candidate genes that might be involved in disease pathogenesis based on functional plausibility and their putative role in IBD carcinogenesis. Polyadenylated mRNA (PolyA+ mRNA) preparation from inflamed intestinal mucosa of patients with a longstanding history of UC and CD was performed with subsequent hybridization of alpha phosphorus [alpha-32P]-deoxyadenotriphosphate-labeled complementary deoxyribonucleic acid (DNA) populations to nucleic acid arrays. Of 588 different human gene transcripts arrayed, secreted apoptosis-related protein 1 (Sarp1), frizzled (fz) homologues, and disheveled (dvl) were differentially expressed, being elevated in UC as compared to CD. These genes encode proteins involved in the Wingless-type (Wnt)/beta-catenin signaling pathway. The autonomous expression of Sarp1 and Sarp1-compatible fz receptor genes suggests that the Wnt pathway may be involved in UC carcinogenesis.
Uthoff
S M
SM
Digestive Surgery Research Laboratory, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Eichenberger
M R
MR
Lewis
R K
RK
Fox
M P
MP
Hamilton
C J
CJ
McAuliffe
T L
TL
Grimes
H L
HL
Galandiuk
S
S
D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000094742:Secreted Frizzled-Related Proteins
D017931:DNA Primers; D004273:DNA, Neoplasm; D008565:Membrane Proteins; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins