Down-regulation in human cancers of DRHC, a novel helicase-like gene from 17q25.1 that inhibits cell growth.

Abstract

Frequent observations of allelic loss in chromosomal band 17q25.1 in a variety of human cancers have suggested that one or more tumor suppressor genes are normally present in this region. Moreover, a locus responsible for hereditary focal non-epidermolytic palmoplantar keratoderma (tylosis oesophageal cancer; TOC), a condition associated with esophageal cancer, has been mapped to the same band. During efforts to sequence, by shot-gun methods, a 1 Mb target region that we had defined as the DNA segment harboring the putative tumor suppressor gene(s) involved in these events, we identified a novel cDNA, DRHC (down-regulated in human cancers), that showed reduced expression in 28 of 95 (29%) cell lines derived from a variety of human cancers. The full-length cDNA, 6275 bp long, was expressed predominantly in thymus and brain. The predicted 1942-amino-acid product exhibited significant sequence homology to yeast enzymes belonging to the DEAD-helicase superfamily, and appeared to be a Uvr/Rep helicase with a DEXDc consensus domain. Transfection of a DRHC expression vector inhibited growth of cancer cells in liquid medium or soft agar. The results suggest that loss of expression of DRHC may play a role in human carcinogenesis.

• Authors: H Nagai, A Yabe, N Mine, I Mikami, H Fujiwara, Y Terada, A Hirano, M Tsuneizumi, T Yokota, M Emi
• Journal: Cancer letters (Cancer Lett) Vol. 193 Issue 1 Pg. 41-7 (Apr 10 2003) ISSN: 0304-3835 [Print] Ireland
• PMID: 12691822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Neoplasm Proteins
• DNA
• DNA Helicases
• MAPK4 protein, human
• RNA Helicases

Topics

• Blotting, Northern
• Brain (metabolism)
• Cell Division
• Chromosomes, Human, Pair 17
• Cloning, Molecular
• DNA (metabolism)
• DNA Helicases (biosynthesis, genetics, metabolism)
• DNA, Complementary (metabolism)
• Databases as Topic
• Down-Regulation
• Esophageal Neoplasms (genetics, metabolism)
• Genes, Tumor Suppressor
• Genetic Vectors
• Humans
• Models, Genetic
• Neoplasm Proteins
• Neoplasms (genetics, metabolism)
• Polymorphism, Single-Stranded Conformational
• Protein Structure, Tertiary
• RNA Helicases
• Reverse Transcriptase Polymerase Chain Reaction
• Thymus Gland (metabolism)
• Time Factors
• Transfection
• Tumor Cells, Cultured