Daigo Y, Nishiwaki T, Kawasoe T, Tamari M, Tsuchiya E, Nakamura Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan.
Cancer Res. 1999 Apr 15;59(8):1966-72.
The short arm of chromosome 3 is thought to contain multiple tumor suppressor genes, because one copy of this chromosomal arm frequently is missing in carcinomas that have arisen in a variety of tissues. We have isolated a novel gene encoding a 1755-amino acid polypeptide, through large-scale sequencing of genomic DNA at 3p21.3. Mutational analysis of this gene by reverse transcription-PCR revealed the lack of functional transcripts and an increase of nonfunctional RNA transcripts in a significant proportion (33%) of cancer cell lines and primary cancers (4 of 14 esophageal cancer cell lines, 2 of 2 renal cancer cell lines, 11 of 30 primary non-small cell lung cancers, and 3 of 10 primary squamous cell carcinomas of the esophagus). However, no alterations of the gene itself were detected in any of the cancers examined. Introduction of the cDNA significantly suppressed the growth of four different cancer cell lines, two of which produced no normal transcript on their own. No such effect occurred when antisense cDNA, cDNA corresponding to an aberrant transcript, or the vector DNA alone were transfected. These data suggest that aberrant transcription of this gene, designated DLC1 (deleted in lung cancer 1), may be involved in carcinogenesis of the lung, esophagus, and kidney.
3号染色体的短臂被认为含有多个肿瘤抑制基因，因为在多种组织发生的癌中，这条染色体臂的一个拷贝常常缺失。我们通过对3p21.3处的基因组DNA进行大规模测序，分离出了一个编码1755个氨基酸多肽的新基因。通过逆转录-聚合酶链反应对该基因进行突变分析发现，在相当比例（33%）的癌细胞系和原发性癌症（14个食管癌细胞系中的4个、2个肾癌细胞系中的2个、30个原发性非小细胞肺癌中的11个以及10个原发性食管鳞状细胞癌中的3个）中，缺乏功能性转录本且非功能性RNA转录本增加。然而，在所检测的任何癌症中均未检测到该基因本身的改变。导入该cDNA可显著抑制四种不同癌细胞系的生长，其中两种癌细胞系自身不产生正常转录本。当转染反义cDNA、对应异常转录本的cDNA或单独的载体DNA时，未出现这种效应。这些数据表明，这个名为DLC1（肺癌缺失1）的基因的异常转录可能参与了肺癌、食管癌和肾癌的致癌过程。
