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A gene has been described, Down Regulated in Adenoma (dra), which is expressed in normal colon but is absent
in the majority of colon adenomas and adenocarcinomas. However, the
function of this protein is unknown. Because of sequence similarity to
a recently cloned membrane sulfate transporter in rat liver, the
transport function of Dra was examined. We established that dra encodes for a Na
Volume 270,
Number 20,
Issue of May 19, pp. 11897-11902, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
-independent transporter for both
sulfate and oxalate using microinjected Xenopus oocytes as an
assay system. Sulfate transport was sensitive to the anion exchange
inhibitor DIDS (4,4`-diisothiocyano-2,2`disulfonic acid stilbene).
Using an RNase protection assay, we found that dra mRNA
expression is limited to the small intestine and colon in mouse,
therefore identifying Dra as an intestine-specific sulfate transporter.
dra also had a unique pattern of expression during intestinal
development. Northern blot analysis revealed a low level of expression
in colon at birth with a marked increase in the first 2 postnatal
weeks. In contrast, there was a lower, constant level of expression in
small intestine in the postnatal period. Caco-2 cells, a colon
carcinoma cell line that differentiates over time in culture,
demonstrated a marked induction of dra mRNA as cells
progressed from the preconfluent (undifferentiated) to the
postconfluent (differentiated) state. These results show that Dra is an
intestine-specific Na
-independent sulfate transporter
that has differential expression during colonic development. This
functional characterization provides the foundation for investigation
of the role of Dra in intestinal sulfate transport and in the malignant
phenotype.
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