Isolation and mutational analysis of a novel human cDNA, DEC1 (deleted in esophageal cancer 1), derived from the tumor suppressor locus in 9q32.
The long arm of chromosome 9 is thought to contain one or more putative tumor suppressor genes that are mutated in squamous cell carcinomas. This region shows frequent loss of heterozygosity (LOH) in carcinomas arising in several developmentally related tissues, including the esophagus, head and neck, lung, and urinary bladder. We previously delineated the commonly deleted region in a panel of esophageal squamous cell carcinomas to a approximately 200 kb genomic segment at 9q32. Here we report the isolation of a novel gene, DEC1 (deleted in esophageal cancer 1), from the target region. Mutational analysis of this gene by reverse-transcriptase polymerase chain reaction disclosed significantly reduced expression of DEC1 in 8 of 13 (62%) esophageal cancer cell lines and in 16 of 30 (53%) primary squamous cell carcinomas of the esophagus. However, no genetic alteration was detected in any of the cancers examined. Introduction of DEC1 cDNA into 3 cancer cell lines that lacked expression of DEC1 significantly suppressed cell growth, whereas antisense cDNA or the vector DNA alone did not. Given the reduced expression of the DEC1 gene in esophageal cancer, the high frequency of LOH at 9q32 in esophageal carcinomas, and the fact that the DEC1 cDNA can suppress growth of some cancer cells in vitro, we suggest that the DEC1 gene is a candidate tumor suppressor in 9q32. Genes Chromosomes Cancer 27:169-176, 2000.
Nishiwaki
T
T
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Daigo
Y
Y
Kawasoe
T
T
Nakamura
Y
Y
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D018288:Carcinoma, Small Cell / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D004938:Esophageal Neoplasms / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins
C403671:DELEC1 protein, human; D018076:DNA, Complementary; D005839:Gentamicins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C010680:antibiotic G 418