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    Characterized BRCA1 and BRCA2 proteins and screening and therapeutic methods based on characterized BRCA1 and BRCA2 proteins
    1.
    发明授权
    Characterized BRCA1 and BRCA2 proteins and screening and therapeutic methods based on characterized BRCA1 and BRCA2 proteins 失效
    表征BRCA1和BRCA2蛋白以及基于特征的BRCA1和BRCA2蛋白的筛选和治疗方法

    公开(公告)号：US06149903A

    公开(公告)日：2000-11-21

    申请号：US99753

    申请日：1998-06-18

    申请人： Jeffrey T. Holt ,  Roy A. Jensen ,  Mary-Claire King ,  David L. Page ,  Csilla I. Szabo ,  Thomas L. Jetton ,  Cheryl L. Robinson-Benion ,  Marilyn E. Thompson

    发明人： Jeffrey T. Holt ,  Roy A. Jensen ,  Mary-Claire King ,  David L. Page ,  Csilla I. Szabo ,  Thomas L. Jetton ,  Cheryl L. Robinson-Benion ,  Marilyn E. Thompson

    IPC分类号： A61K38/00 ,  A61K48/00 ,  A61K49/00 ,  C07K14/47

    CPC分类号： A61K49/0004 ,  C07K14/4703 ,  A61K38/00 ,  A61K48/00 ,  C07K2319/00

    摘要： Genetic analysis of familial breast and ovarian cancer indicates that BRCA1 is a tumor suppressor gene. The BRCA1 gene encodes a 190 kDa protein with sequence homology and biochemical analogy to the granin family of proteins. Granins are secreted from endocrine cells via the regulated secretory pathway and are proteolytically cleaved to yield biologically active peptides. BRCA1 protein localizes to secretory vesicles, and was demonstrated to be secreted. Gene transfer of BRCA1 inhibits growth and tumorigenesis of breast and ovarian cancer cells, but not colon or lung cancer cells or fibroblasts, suggesting that BRCA1 encodes a tissue-specific growth inhibitor. Thus, BRCA1 is a secreted growth inhibitor and functions by a mechanism not previously described for tumor suppressor genes. The BRCA2 breast and ovarian cancer gene encodes a protein that also includes a granin region, indicating that the BRCA2 protein is also a secreted tumor suppressor. Therapeutic methods using the BRCA1 and BRCA proteins and genes are also described. A method of screening for the receptors of the BRCA1 protein and BRCA2 proteins is also described.

    摘要翻译： 家族性乳腺癌和卵巢癌的遗传分析表明BRCA1是肿瘤抑制基因。 BRCA1基因编码190 kDa的蛋白质，与蛋白质的大豆蛋白家族具有序列同源性和生物化学类比。 通过经调节的分泌途径从内分泌细胞分泌颗粒，并被蛋白水解切割以产生生物活性肽。 BRCA1蛋白定位于分泌囊泡，并被证明是分泌的。 BRCA1的基因转移抑制乳腺和卵巢癌细胞的生长和肿瘤发生，但不抑制结肠或肺癌细胞或成纤维细胞，这表明BRCA1编码组织特异性生长抑制剂。 因此，BRCA1是分泌的生长抑制剂，并且通过以前未被描述用于肿瘤抑制基因的机制起作用。 BRCA2乳腺癌和卵巢癌基因编码的蛋白质也包括一个颗粒蛋白质区域，表明BRCA2蛋白也是分泌的肿瘤抑制因子。 还描述了使用BRCA1和BRCA蛋白和基因的治疗方法。 还描述了筛选BRCA1蛋白和BRCA2蛋白的受体的方法。

    Method for detection and treatment of breast cancer
    4.
    发明授权
    Method for detection and treatment of breast cancer 失效
    检测和治疗乳腺癌的方法

    公开(公告)号：US06342483B1

    公开(公告)日：2002-01-29

    申请号：US09007678

    申请日：1998-01-15

    申请人： Jeffrey T. Holt ,  Roy A. Jensen ,  David L. Page ,  Patrice S. Obermiller ,  Cheryl L. Robinson-Benion ,  Marilyn E. Thompson

    发明人： Jeffrey T. Holt ,  Roy A. Jensen ,  David L. Page ,  Patrice S. Obermiller ,  Cheryl L. Robinson-Benion ,  Marilyn E. Thompson

    IPC分类号： A61K4800

    CPC分类号： G01N33/57415 ,  C07K14/82 ,  C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158

    摘要： The present invention provides a method of detecting and diagnosing pre-invasive breast cancer by identifying differentially expressed genes in early, pre-invasive breast cancer tissue. Differentially expressed genes can be used as genetic markers to indicate the presence of pre-invasive cancerous tissues. Microscopically-directed tissue sampling techniques combined with differential display or differential screening of cDNA libraries are used to determine differential expression of genes in the early stages of breast cancer. Differential expression of genes in preinvasive breast cancer tissue is confirmed by RT-PCR, nuclease protection assays and in-situ hybridization of ductal carcinoma in situ tissue RNA and control tissue RNA. The present invention also provides a method of screening for compounds that induce expression of the BRCA1 gene, whose product negatively regulates cell growth in both normal and malignant mammary epithlial cells. The present invention also relates to gene therapy method using this gene.

    摘要翻译： 本发明提供了一种通过在早期浸润性乳腺癌组织中识别差异表达的基因来检测和诊断浸润性乳腺癌的方法。 差异表达的基因可用作遗传标记，以指示侵入性癌组织的存在。 使用与差异显示或差异筛选cDNA文库的显微指导组织取样技术来确定乳腺癌早期基因的差异表达。 通过RT-PCR，核酸酶保护试验和导管癌原位组织RNA和对照组织RNA的原位杂交证实了侵袭性乳腺癌组织中基因的差异表达。 本发明还提供了筛选诱导BRCA1基因表达的化合物的方法，所述BRCA1基因的产物负调节正常和恶性乳腺上皮细胞中的细胞生长。 本发明还涉及使用该基因的基因治疗方法。