title: Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers.
abstract: The human cysteine dioxygenase 1 (CDO1) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinate, and plays a key role in taurine biosynthesis. In our search for novel methylated gene promoters, we have analyzed differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of 5-aza-2'-deoxycytidine. Among the genes identified, the CDO1 promoter was found to be differentially methylated in primary CRC tissues with high frequency compared to normal colon tissues. In addition, a statistically significant difference in the frequency of CDO1 promoter methylation was observed between primary normal and tumor tissues derived from breast, esophagus, lung, bladder and stomach. Downregulation of CDO1 mRNA and protein levels were observed in cancer cell lines and tumors derived from these tissue types. Expression of CDO1 was tightly controlled by promoter methylation, suggesting that promoter methylation and silencing of CDO1 may be a common event in human carcinogenesis. Moreover, forced expression of full-length CDO1 in human cancer cells markedly decreased the tumor cell growth in an in vitro cell culture and/or an in vivo mouse model, whereas knockdown of CDO1 increased cell growth in culture. Our data implicate CDO1 as a novel tumor suppressor gene and a potentially valuable molecular marker for human cancer.
authors.affiliation: Department of Otolaryngology, Head and Neck Cancer Research Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Mariana
authors.initials: M
authors.lastname: Brait
authors.forename: Shizhang
authors.initials: S
authors.lastname: Ling
authors.forename: Jatin K
authors.initials: JK
authors.lastname: Nagpal
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chang
authors.forename: Hannah Lui
authors.initials: HL
authors.lastname: Park
authors.forename: Juna
authors.initials: J
authors.lastname: Lee
authors.forename: Jun
authors.initials: J
authors.lastname: Okamura
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050558:Cysteine Dioxygenase / Q000172:deficiency / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*
chemical_list: D050558:Cysteine Dioxygenase