This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Daigo, Y. Articles by Nakamura, Y. Search for Related Content PubMed PubMed Citation Articles by Daigo, Y. Articles by Nakamura, Y.

Molecular Cloning of a Candidate Tumor Suppressor Gene, DLC1, from Chromosome 3p21.3¹

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108, Japan [Y. D., T. N., T. K., M. T., Y. N.], and Department of Pathology, Saitama Cancer Center Research Institute, Saitama, Japan [E. T.]

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.

This article has been cited by other articles:

				L. Fu, Y.-R. Qin, D. Xie, L. Hu, D. L. Kwong, G. Srivastava, S. W. Tsao, and X.-Y. Guan Characterization of a Novel Tumor-Suppressor Gene PLC{delta}1 at 3p22 in Esophageal Squamous Cell Carcinoma Cancer Res., November 15, 2007; 67(22): 10720 - 10726. [Abstract] [Full Text] [PDF]

				M. P. Hitchins, V. A. Lin, A. Buckle, K. Cheong, N. Halani, S. Ku, C.-T. Kwok, D. Packham, C. M. Suter, A. Meagher, et al. Epigenetic Inactivation of a Cluster of Genes Flanking MLH1 in Microsatellite-Unstable Colorectal Cancer Cancer Res., October 1, 2007; 67(19): 9107 - 9116. [Abstract] [Full Text] [PDF]

				T. Rauch, H. Li, X. Wu, and G. P. Pfeifer MIRA-Assisted Microarray Analysis, a New Technology for the Determination of DNA Methylation Patterns, Identifies Frequent Methylation of Homeodomain-Containing Genes in Lung Cancer Cells Cancer Res., August 15, 2006; 66(16): 7939 - 7947. [Abstract] [Full Text] [PDF]

				A. L.S. Tai, W. Mak, P. K.M. Ng, D. T.T. Chua, M. Y.M. Ng, L. Fu, K. K.W. Chu, Y. Fang, Y. Qiang Song, M. Chen, et al. High-throughput Loss-of-Heterozygosity Study of Chromosome 3p in Lung Cancer Using Single-Nucleotide Polymorphism Markers. Cancer Res., April 15, 2006; 66(8): 4133 - 4138. [Abstract] [Full Text] [PDF]

				J. N. ANDERSEN, P. G. JANSEN, S. M. ECHWALD, O. H. MORTENSEN, T. FUKADA, R. DEL VECCHIO, N. K. TONKS, and N. P. H. MOLLER A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage FASEB J, January 1, 2004; 18(1): 8 - 30. [Abstract] [Full Text] [PDF]

				S Dasgupta, S B Chakraborty, A Roy, S Roychowdhury, and C K Panda Differential deletions of chromosome 3p are associated with the development of uterine cervical carcinoma in Indian patients Mol. Pathol., October 1, 2003; 56(5): 263 - 269. [Abstract] [Full Text] [PDF]

				M. Kost-Alimova, H. Kiss, L. Fedorova, Y. Yang, J. P. Dumanski, G. Klein, and S. Imreh Coincidence of synteny breakpoints with malignancy-related deletions on human chromosome 3 PNAS, May 27, 2003; 100(11): 6622 - 6627. [Abstract] [Full Text] [PDF]

				A. Protopopov, V. Kashuba, V. I. Zabarovska, O. V. Muravenko, M. I. Lerman, G. Klein, and E. R. Zabarovsky An Integrated Physical and Gene Map of the 3.5-Mb Chromosome 3p21.3 (AP20) Region Implicated in Major Human Epithelial Malignancies Cancer Res., January 15, 2003; 63(2): 404 - 412. [Abstract] [Full Text] [PDF]

				F. Sukosd, N. Kuroda, T. Beothe, A. P. Kaur, and G. Kovacs Deletion of Chromosome 3p14.2-p25 Involving the VHL and FHIT Genes in Conventional Renal Cell Carcinoma Cancer Res., January 15, 2003; 63(2): 455 - 457. [Abstract] [Full Text] [PDF]

				Y. Tomizawa, T. Kohno, H. Kondo, A. Otsuka, M. Nishioka, T. Niki, T. Yamada, A. Maeshima, K. Yoshimura, R. Saito, et al. Clinicopathological Significance of Epigenetic Inactivation of RASSF1A at 3p21.3 in Stage I Lung Adenocarcinoma Clin. Cancer Res., July 1, 2002; 8(7): 2362 - 2368. [Abstract] [Full Text] [PDF]

				T. Kuroki, F. Trapasso, T. Shiraishi, H. Alder, K. Mimori, M. Mori, and C. M. Croce Genetic Alterations of the Tumor Suppressor Gene WWOX in Esophageal Squamous Cell Carcinoma Cancer Res., April 1, 2002; 62(8): 2258 - 2260. [Abstract] [Full Text] [PDF]

				G. D. Stoner and A. Gupta Etiology and chemoprevention of esophageal squamous cell carcinoma Carcinogenesis, November 1, 2001; 22(11): 1737 - 1746. [Abstract] [Full Text] [PDF]

				G. Marra, S. D'Atri, C. Corti, L. Bonmassar, M. S. Cattaruzza, P. Schweizer, K. Heinimann, Z. Bartosova, M. Nystrom-Lahti, and J. Jiricny Tolerance of human MSH2+/- lymphoblastoid cells to the methylating agent temozolomide PNAS, June 19, 2001; 98(13): 7164 - 7169. [Abstract] [Full Text] [PDF]

				M. Fujita, Y. Furukawa, Y. Nagasawa, M. Ogawa, and Y. Nakamura Down-Regulation of Monocyte Chemotactic Protein-3 by Activated {beta}-Catenin Cancer Res., December 1, 2000; 60(23): 6683 - 6687. [Abstract] [Full Text]

				K. Sano, A. Hayakawa, J.-H. Piao, Y. Kosaka, and H. Nakamura Novel SH3 protein encoded by the AF3p21 gene is fused to the mixed lineage leukemia protein in a therapy-related leukemia with t(3;11) (p21;q23) Blood, February 1, 2000; 95(3): 1066 - 1068. [Abstract] [Full Text] [PDF]