[Clinical application of alternative splicing form of c-myc suppressor FUSE-binding protein-interacting repressor for cancer detection and treatment].
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.
Matsushita
Kazuyuki
K
Department of Molecular Diagnosis & Division of Clinical Genetics and Proteomics, Graduate School of Medicine, Chiba University, Japan. kmatsu@faculty.chiba-u.jp
Kajiwara
Toshiko
T
Itoga
Sakae
S
Satoh
Mamoru
M
Sogawa
Kazuyuki
K
Umemura
Hiroshi
H
Sawai
Setsu
S
Nishimura
Motoi
M
Tamura
Mai
M
Tanaka
Nobuko
N
Shimada
Hideaki
H
Tomonaga
Takeshi
T
Nomura
Fumio
F
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
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