Down-regulation in human cancers of DRHC, a novel helicase-like gene from 17q25.1 that inhibits cell growth.
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.
Nagai
H
H
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School. 1-396, Kosugi-cho, Nakahara-ku, Kawasaki 211-0063, Japan.
Yabe
A
A
Mine
N
N
Mikami
I
I
Fujiwara
H
H
Terada
Y
Y
Hirano
A
A
Tsuneizumi
M
M
Yokota
T
T
Emi
M
M
D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002455:Cell Division; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006801:Humans; D008957:Models, Genetic; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D020365:RNA Helicases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D004247:DNA; D004265:DNA Helicases; C562219:MAPK4 protein, human; D020365:RNA Helicases