title: [Clinical application of alternative splicing form of c-myc suppressor FUSE-binding protein-interacting repressor for cancer detection and treatment].
abstract: Development of useful biomarkers is pivotal for prediction of micro-metastasis, recurrence probability and/or prognosis of the patients. Recent studies have revealed that cancer-specific alternative splicing can be valuable for cancer cell detection. Among them, FUSE-binding protein-interacting repressor, FIR, has been reported to repress c-myc transcription and its exon2-spliced variant, FIRDelta(exon)2, is unable to repress c-myc by competing with authentic FIR in vivo and in vitro. Moreover FIRDelta(exon)2 was frequently discovered in human primary colorectal cancers, but not in the adjacent normal tissues, indicating its cancer-related expression. Thus, the expression level of FIRDelta(exon)2 mRNA in the colorectal cancer tissues as tumor marker candidates is examined. Further, to determine the interacting proteins, FIR-flag or FIRDelta(exon)2-flag stably expressing HeLa cells have been established by G418 selection and nuclear proteins were co immunoprecipitated with flag-conjugated magnetic beads. Those co-immunoprecipitated proteins with FIR or FIRDelta(exon)2 are candidates of tumor makers. In addition, substances that interfers FIR mRNA splicing should be anti-cancer drugs. Together, FIR splicing variant, FIRDelta(exon)2 mRNA or proteins and its interacting proteins are applicable for novel screening tumor markers in colorectal cancer detection.
authors.affiliation: Department of Molecular Diagnosis & Division of Clinical Genetics and Proteomics, Graduate School of Medicine, Chiba University, Japan. kmatsu@faculty.chiba-u.jp
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsushita
authors.forename: Toshiko
authors.initials: T
authors.lastname: Kajiwara
authors.forename: Sakae
authors.initials: S
authors.lastname: Itoga
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Umemura
authors.forename: Setsu
authors.initials: S
authors.lastname: Sawai
authors.forename: Motoi
authors.initials: M
authors.lastname: Nishimura
authors.forename: Mai
authors.initials: M
authors.lastname: Tamura
authors.forename: Nobuko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tomonaga
authors.forename: Fumio
authors.initials: F
authors.lastname: Nomura
mesh_terms: D017398:Alternative Splicing; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D004268:DNA-Binding Proteins; D004354:Drug Screening Assays, Antitumor; D005091:Exons; D016259:Genes, myc / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C410595:poly-U binding splicing factor 60KDa