Abstract
Prostaglandin E~2~ (PGE~2~) plays an important role in protection of the gastric mucosa against various damaging agents and growth‐inhibitory activity on tumor cells. However, the precise regulation mechanism of PGE~2~ in gastric cancer cells is still unclear. In this study, we isolated a gene, which is regulated by PGE~2~ in SNU‐1, human gastric adenocarcinoma cells, using differential display RT‐PCR (DD RT‐PCR) and characterized the function of the gene induced by PGE~2~. The full‐length cDNA of the gene was cloned by the rapid amplification of cDNA ends method. The 1659 base pair cDNA consists of a 30‐nt 5′‐noncoding region, an 891‐nt open reading frame and a 738‐nt 3′noncoding region that includes a poly (A) signal. As a result of protein motif search, we found that it has a conserved thioredoxin‐active site, Cys‐Gly‐Pro‐Cys and a Myb‐DNA binding domain repeat signature. Thus, we designated this gene product as thioredoxin‐related protein‐1, TRP‐1. TRP‐1 was expressed in a lower extent in renal, gastric and colon cancer tissues and is translated into 33 kDa protein in nuclear and cytoplasmic fractions. TRP‐1 has a thioredoxin activity, which was detected using the insulin disulfide reduction assay. Another potential role of TRP‐1 is repression of B‐Myb activity through direct binding to B‐Myb, a transcriptional factor induced at G1–S transition. Finally, TRP‐1 overexpression inhibits mammalian cell proliferation and specifically predispose to G0/G1 phase arrest. In conclusion, these results imply that TRP‐1 is a mammalian thioredoxin and plays as a transcriptional repressor through direct binding to the transcription factor B‐Myb. © 2005 Wiley‐Liss, Inc.