Screening assays for cancer chemopreventative agents
    92.
    发明授权
    Screening assays for cancer chemopreventative agents 失效
    癌症化学预防剂的筛选试验

    公开(公告)号:US5874235A

    公开(公告)日:1999-02-23

    申请号:US896462

    申请日:1997-07-18

    CPC分类号: G01N33/5011

    摘要: Nonsteroidal anti-inflammatory drugs cause a dramatic increase in intracellular ceramide, which induces apoptosis. The ceramide increase is likely mediated by cyclooxygenase inhibition, which elevates arachidonic acid, which stimulates sphingomyelinase, which produces ceramide. Contacting members of this pathway with test compounds and observing their effects provides a method of screening for potential cancer chemopreventative agents.

    摘要翻译: 非甾体抗炎药引起细胞内神经酰胺的剧烈增加,诱导细胞凋亡。 神经酰胺增加可能由环氧合酶抑制介导,其升高花生四烯酸,其刺激产生神经酰胺的鞘磷脂酶。 将该途径与测试化合物接触并观察其作用提供了筛选潜在的癌症化学预防剂的方法。

    .beta.-catenin, Tcf-4, and APC interact to prevent cancer
    94.
    发明授权
    .beta.-catenin, Tcf-4, and APC interact to prevent cancer 失效
    β-联蛋白,Tcf-4和APC相互作用以预防癌症

    公开(公告)号:US5851775A

    公开(公告)日:1998-12-22

    申请号:US821355

    申请日:1997-03-20

    摘要: The APC tumor suppressor protein binds to .beta.-catenin, a protein recently shown to interact with Tcf/Lef transcription factors. Here, the gene encoding a Tcf family member that is expressed in colonic epithelium (hTcf-4) was cloned and characterized. hTcf-4 transactivates transcription only when associated with .beta.-catenin. Nuclei of APC.sup.-/- colon carcinoma cells were found to contain a stable .beta.-catenin-hTCF-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed .beta.-catenin from hTcf4 and abrogated the transcriptional transactivation. Constitutive transcription of TCF target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium. It is also shown here that the products of mutant APC genes found in colorectal tumors are defective in regulating .beta.-catenin/Tcf-4 transcrpitional activation. Furthermore, colorectal tumors with intact APC genes were shown to contain subtle activating mutations of .beta.-catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of .beta.-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or .beta.-catenin.

    摘要翻译: APC肿瘤抑制蛋白结合β-连环蛋白,最近显示出与Tcf / Lef转录因子相互作用的蛋白质。 这里,克隆并表征编码在结肠上皮(hTcf-4)中表达的Tcf家族成员的基因。 hTcf-4仅在与β-连环蛋白相关时才转录转录。 发现APC - / - 结肠癌细胞的核含有稳定的β-联蛋白-hTCF-4复合物,其通过Tcf报道基因的转录测量而具有组成型活性。 重新引入APC从hTcf4中除去β-连环蛋白,并废除转录反式激活。 由APC功能丧失引起的TCF靶基因的组成转录可能是结肠上皮早期转化的关键事件。 这里还显示,在结肠直肠肿瘤中发现的突变APC基因的产物在调节β-连环蛋白/ Tcf-4跨刺激激活中是有缺陷的。 此外,具有完整APC基因的结肠直肠肿瘤显示含有改变功能显着磷酸化位点的β-连环蛋白的微妙活化突变。 这些结果表明,β-连环蛋白的调节对于APC的肿瘤抑制作用至关重要,并且该调节可以通过APC或β-连环蛋白的突变来规避。

    Human JTV1 gene overlaps PMS2 gene
    95.
    发明授权
    Human JTV1 gene overlaps PMS2 gene 失效
    人JTV1基因与PMS2基因重叠

    公开(公告)号:US5843757A

    公开(公告)日:1998-12-01

    申请号:US518862

    申请日:1995-08-24

    CPC分类号: C07K14/47

    摘要: The hPMS2 gene encodes a protein which is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published hPMS2 cDNA sequence lacks an upstream in-frame stop codon preceding the presumptive initiating methionine. To further evaluate the 5' terminus of the hPMS2 coding region, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5' genomic segment of the hPMS2 locus. The hPMS2 gene transcripts were found to have heterogeneous but collinear 5' termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5 kDa polypeptide was found to transcriptionally initiate within hPMS2 from the opposite strand.

    摘要翻译: hPMS2基因编码参与DNA错配修复的蛋白质,并在遗传性非息肉性结肠癌(HNPCC)患者的亚组中突变。 以前发表的hPMS2 cDNA序列在推定的起始甲硫氨酸之前缺少上游的内切终止密码子。 为了进一步评估hPMS2编码区的5'末端,我们分离了另外的cDNA克隆,RT-PCR产物和hPMS2基因座的相应的5'基因组片段。 发现hPMS2基因转录物具有异源但共线的5'末端,其中之一包含起始甲硫氨酸之前的框内终止密码子。 另外,发现编码34.​​5kDa多肽的新基因在相反链的hPMS2内转录起始。

    EBI nucleic acids
    97.
    发明授权
    EBI nucleic acids 失效
    EBI核酸

    公开(公告)号:US5736389A

    公开(公告)日:1998-04-07

    申请号:US446919

    申请日:1995-05-22

    摘要: Inactivation of the APC minor suppressor gene plays an important role in the development of both sporadic and familial forms of colorectal cancers. The majority of these mutations result in the loss of the carboxyl terminus of the APC protein. A cellular protein, EB1, that associates with the carboxyl terminus of APC both in vitro and in vivo has been identified. The EB1 gene is predicted to encode a 268 amino acid protein without significant homology to any protein with known function.

    摘要翻译: APC次要抑制基因的失活在结肠直肠癌的散发和家族形式的发展中起重要作用。 这些突变中的大多数导致APC蛋白的羧基末端的损失。 已经鉴定了在体外和体内与APC的羧基末端缔合的细胞蛋白质EB1。 EB1基因被预测编码268个氨基酸的蛋白质,而与具有已知功能的任何蛋白质没有显着的同源性。

    Method for serial analysis of gene expression
    98.
    发明授权
    Method for serial analysis of gene expression 失效
    基因表达序列分析方法

    公开(公告)号:US5695937A

    公开(公告)日:1997-12-09

    申请号:US527154

    申请日:1995-09-12

    摘要: Serial analysis of gene expression, SAGE, a method for the rapid quantitative and qualitative analysis of transcripts is provided. Short defined sequence tags corresponding to expressed genes are isolated and analyzed. Sequencing of over 1,000 defined tags in a short period of time (e.g., hours) reveals a gene expression pattern characteristic of the function of a cell or tissue. Moreover, SAGE is useful as a gene discovery tool for the identification and isolation of novel sequence tags corresponding to novel transcripts and genes.

    摘要翻译: 提供基因表达的串行分析,SAGE,一种用于快速定量和定性分析转录本的方法。 分离并分析与表达基因相对应的短定义序列标签。 在短时间(例如,小时)内测定超过1,000个定义的标签显示了细胞或组织功能特征的基因表达模式。 此外,SAGE可用作用于鉴定和分离对应于新转录物和基因的新序列标签的基因发现工具。