HER-2/NEU ALTERATIONS IN BREAST AND OVARIAN CANCER

乳腺癌和卵巢癌中的 HER-2/NEU 改变

• 批准号: 6327587
• 负责人: DENNIS J SLAMON
• 金额: $ 18.15万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-22 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6327587
• 关键词: athymic mouse; breast neoplasms; complementary DNA; estrogens; gel electrophoresis; gene induction /repression; gene mutation; genetic library; metastasis; neoplasm /cancer genetics; neoplastic process; ovary neoplasms; protein tyrosine kinase; protooncogene

Human breast and ovarian cancer together account for 162,000 new cases of cancer per year or essentially one third of all cancers occurring in women. In addition, they account for 55,000 deaths per year, or essentially one quarter of cancer related deaths in women. The HER-2/neu proto-oncogene is a putative growth factor receptor which is related to, but distinct from the epidermal growth factor receptor. Studies done in our laboratory have shown that this gene is amplified and/or overexpressed in ~30% of human breast and ovarian cancers. Moreover, this alteration is associated with a poor clinical outcome for patients in whose tumors it occurs. The objective of this proposal is to investigate the possible role this alteration plays in the pathogenesis of these diseases. Transfection studies will be done to convert human breast and ovarian cells from cells with a single copy and low levels of expression of the HER-2/neu gene to cells with an amplified/overexpressed gene mimicking the alteration found in human breast and ovarian cancer. The biologic effects of this alteration will be investigated, including effects on DNA synthesis, cell growth, cell invasiveness, and tumorigenicity in the nude mouse. In addition, antibodies to extracellular domains of this gene product will be used in vitro and in vivo studies of cells containing this alteration to determine if the antibodies change the biologic effects mediated by this alteration. These studies may lead to development of novel therapeutic approaches to these diseases based on this oncogene alteration.

人类乳腺癌和卵巢癌共同考虑了162,000例新病例 每年癌症或本质上三分之一发生的癌症。 此外，它们每年造成55,000人死亡，或者本质上是一个 女性癌症相关的四分之一。 HER-2/NEU原始癌基因是 推定的生长因子受体，与 表皮生长因子受体。 在我们的实验室进行的研究 表明该基因在约30％的人中被扩增和/或过表达 乳腺癌和卵巢癌。 此外，此更改与 对于发生肿瘤的患者而言，临床结果不佳。 这 该提议的目的是调查这可能的作用 改变这些疾病的发病机理。 转染 将进行研究以转化从细胞中的人乳房和卵巢细胞 Her-2/neu基因的单个副本和低水平的表达 具有放大/过表达基因的细胞模仿发现的改变 在人类乳腺癌和卵巢癌中。 生物学效应 将研究改变，包括对DNA合成的影响 裸鼠的生长，细胞侵入性和肿瘤性。 在 此外，该基因产物的细胞外结构域的抗体将是 在体外和体外研究中，对包含这种改变的细胞进行了 确定抗体是否改变了由此介导的生物学作用 改造。 这些研究可能导致新的治疗性发展 基于这种癌基因的改变来解决这些疾病。