Down-regulation of the down-regulated in adenoma (DRA) gene correlates with colon tumor progression.
The down-regulated in adenoma (DRA) gene was originally identified as a gene that was down-regulated in colon tumors. It encodes a protein with anion transporter function that is expressed predominantly in the mucosa of the lower gastrointestinal tract. In this study, expression of DRA and its cellular distribution have been investigated in a series of benign adenomatous polyps and malignant colorectal tumors and in corresponding normal colonic mucosa. We show that DRA mRNA and protein are expressed in all normal colonic tissue specimens with the protein restricted primarily to the terminally differentiated columnar epithelium and some goblet cells. Apical membrane localization was especially apparent in the columnar epithelium. The levels of DRA mRNA transcripts were down-regulated in all colon tumors examined relative to matched normal mucosa, with most specimens showing undetectable levels of DRA mRNA (77 of 104 tumors). DRA down-regulation was positively associated with colonic tumor progression according to Dukes' stage and was particularly significant in the early transition from normal mucosa to polyp to adenocarcinoma. DRA expression does not appear to be strictly associated with colonic cell differentiation; rather, its absence and down-regulation were associated with the proliferating component of the crypt epithelium and with neoplastic transformation, respectively.
Molecular Oncology Laboratory, Queensland Cancer Fund Experimental Oncology Program, Queensland Institute of Medical Research, Brisbane, Australia.
T M
TM
Antalis
J A
JA
Reeder
D C
DC
Gotley
M K
MK
Byeon
M D
MD
Walsh
K W
KW
Henderson
T S
TS
Papas
C W
CW
Schweinfest
D000236:Adenoma / Q000235:genetics; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism
D002352:Carrier Proteins; D012333:RNA, Messenger