课题基金 / 基金详情

DNA DAMAGE AND GENE EXPRESSION IN BREAST CANCER

DNA DAMAGE AND GENE EXPRESSION IN BREAST CANCER
乳腺癌中的 DNA 损伤和基因表达
批准号:
2096925
负责人:
David A. Gewirtz
金额:
$9.31万
依托单位国家:
美国
项目类别:
财政年份:
1995
资助国家:
美国
项目状态:
已结题
起止时间:
1995-08-16 至 1998-07-31

项目摘要

项目成果

David A. Gewirtz的其他基金

相似基金

相关文献

中文摘要
翻译
介导细胞静止的生化和分子扰动 而破坏DNA的抗肿瘤药物的细胞毒性作用 明白了。本申请中提出的研究是基于 C-myc基因表达下调的假设 癌基因与myc癌蛋白水平和活性的变化 可能是一条生长停滞反应途径的关键组成部分 MCF-7乳腺癌细胞DNA损伤。为了检验这一假设, 我们建议证明用c-myc基因转导MCF-7细胞 由构成启动子驱动的构建减少或取消 对拓扑异构酶II抑制剂VM-26和m-AMSA的敏感性; 相比之下,类似的K562人白血病细胞(其中c-myc 似乎与增长监管无关),符合宪法 C-myc的表达应该不会改变细胞对这些药物的敏感性。这个 C-myc下调的性质将通过区分 Vm-26和m-AMSA在转录水平的作用(转录 起始和延伸)和转录本稳定性;参与 细胞对VM-26和m-AMSA反应中的c-myc启动子区域 将通过使用myc监测药物对CAT活性的影响来建立 将启动子-CAT载体导入MCF-7细胞。联谊会 生长停滞的myc癌蛋白将通过确定 VM-26和m-AMSA对癌蛋白水平、磷酸化的影响 癌蛋白的状态,以及癌蛋白与其共识的结合 序列。测定各种破坏DNA药物的能力(和 电离辐射)以产生c-myc表达的侧向调节 而生长停滞将有助于确定c-myc是否一致 参与MCF-7细胞对DNA损伤的细胞反应。最后, C-myc基因表达下调与生长停滞的关系 对DNA损伤的反应将在其他实验模型中进行评估 乳腺癌的风险。
英文摘要
The biochemical and molecular perturbations which mediate the cytostatic and cytotoxic effects of antineoplastic drugs which damage DNA are not understood. The studies proposed in this application are predicated upon the hypothesis that down regulation of the expression of the c-myc oncogene and alterations in the levels and activity of the myc oncoprotein may be critical components of one pathway of growth arrest in response to DNA damage& in MCF-7 breast tumor cells. In order to test this hypothesis, we propose to demonstrate that transfection of MCF-7 cells with a c-myc construct driven by a constitutive promoter reduces or abrogate sensitivity to the topoisomerase II inhibitors, VM-26 and m-AMSA; in contrast, a similar transfection of K562 human leukemic cells (where c-myc appears to be uninvolved in growth regulation) with constitutively expressed c-myc should fail to alter cell sensitivity to these drugs. The nature of c-myc down-regulation will be defined by discriminating between effects of VM-26 and m-AMSA at the level of transcription (transcript initiation and elongation) and transcript stability; the involvement of the c-myc promoter region in the cellular response to VM-26 and m-AMSA will be established by monitoring drug effects on CAT activity using a myc promoter-CAT construct transfected into MCF-7 cells. The association of the myc oncoprotein with growth arrest 'will be defined by determining the influence of VM-26 and m-AMSA on oncoprotein levels, the phosphorylation state of the oncoprotein, and binding of the oncoprotein to its consensus sequence. Determination of the capacity of various DNA damaging drugs (and ionizing radiation) to produce collateral modulation of c-myc expression and growth arrest will serve to establish whether c-myc is uniformly involved in the cellular response to DNA damage in MCF-7 cells. Finally, the paradigm relating down-regulation of c-myc expression to growth arrest in response to DNA damage will be evaluated in other experimental models of breast cancer.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A sequential therapeutic strategy of senescence induction and senolytics for elimination of surviving residual breast tumor cells
  • 批准号:
    10360542
  • 项目类别:
  • 资助金额:
    $49.92万
  • 财政年份:
    2021
  • 负责人:
    David A. Gewirtz
  • 依托单位:
A sequential therapeutic strategy of senescence induction and senolytics for elimination of surviving residual breast tumor cells
  • 批准号:
    10581513
  • 项目类别:
  • 资助金额:
    $49.92万
  • 财政年份:
    2021
  • 负责人:
    David A. Gewirtz
  • 依托单位:
A sequential therapeutic strategy of senescence induction and senolytics for elimination of surviving residual breast tumor cells
  • 批准号:
    10746519
  • 项目类别:
  • 资助金额:
    $4.39万
  • 财政年份:
    2021
  • 负责人:
    David A. Gewirtz
  • 依托单位:
Use of senolytics to enhance chemotherapeutic efficacy in lung cancer
  • 批准号:
    9765748
  • 项目类别:
  • 资助金额:
    $39.9万
  • 财政年份:
    2019
  • 负责人:
    David A. Gewirtz
  • 依托单位:
海外基金