Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas.
To investigate the mechanisms of colorectal carcinogenesis, we searched for genes regulated by adenomatous polyposis coli gene product (APC) and identified a novel gene, termed HELAD1 (helicase, APC down-regulated 1). A recombinant polypeptide representing the ATPases associated with cellular activities (AAA) domain of the HELAD1 product showed 3' to 5' helicase activity and exonuclease activity in vitro. HELAD1 was abundantly expressed in 16 of 20 colon cancers examined but hardly detectable in corresponding non-cancerous mucosae. Treatment of colon-cancer cells with antisense oligonucleotides suppressed its expression and induced apoptosis. These data revealed an importance of HELAD1 in colorectal carcinogenesis and suggest that suppression of HELAD1 may be a promising therapeutic strategy.
Ishiguro
Hideyuki
H
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku Tokyo 108-8639, Japan.
Shimokawa
Takashi
T
Tsunoda
Tatsuhiko
T
Tanaka
Toshihiro
T
Fujii
Yoshitaka
Y
Nakamura
Yusuke
Y
Furukawa
Yoichi
Y
D015179:Colorectal Neoplasms / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics* / Q000302:isolation & purification; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D004265:DNA Helicases; C465311:NAV2 protein, human