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    • 10. 发明申请
    • METHODS OF DIAGNOSING AND TREATING COLORECTAL CANCER
    • 诊断和治疗彩色癌的方法
    • WO2003085134A2
    • 2003-10-16
    • PCT/JP2003/004226
    • 2003-04-02
    • JAPAN AS REPRESENTED BY THE PRESIDENT OF THE UNIVERSITY OF TOKYOONCOTHERAPY SCIENCE, INC.NAKAMURA, YusukeFURUKAWA, Yoichi
    • NAKAMURA, YusukeFURUKAWA, Yoichi
    • C12Q1/68
    • C12Q1/6809A61K39/00C07K14/47C12N9/90C12Q1/6886
    • The present application provides a human gene, HELAD1, whose expression is markedly elevated in a great majority of colorectal cancers as compared to corresponding non-cancerous tissues. Specifically, in investigating the mechanisms of colorectal carcinogenesis, genes regulated by adenomatous polyposis coli gene product (APC) were searched and the HELAD1 gene (helicase, APC down-regulated 1) was identified. 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. This data demonstrates the importance of HELAD1 in colorectal carcinogenesis and its utility as a diagnostic marker of colorectal cancer. It further suggest that suppression of HELAD1 may be a promising therapeutic strategy in the treatment of colorectal cancer.
    • 本申请提供了一种人类基因HELAD1,与相应的非癌组织相比,其大部分结肠直肠癌中的表达显着升高。 具体来说,在调查结肠直肠癌发生机制中,检索了由腺瘤性息肉病基因产物(APC)调控的基因,并确定了HELAD1基因(解旋酶,APC下调1)。 表达与HELAD1产物的细胞活性(AAA)结构域相关的ATP酶的重组多肽在体外显示出3'至5'的解旋酶活性和外切核酸酶活性。 HELAD1在检查的20个结肠癌中的16个中被大量表达,但在相应的非癌性粘膜中几乎不可检测到。 用反义寡核苷酸治疗结肠癌细胞抑制其表达并诱导凋亡。 该数据表明HELAD1在结肠直肠癌发生中的重要性及其作为结肠直肠癌诊断标志物的作用。 进一步表明,抑制HELAD1可能是治疗结肠直肠癌的有希望的治疗策略。