HER-2/NEU ALTERATIONS IN BREAST AND OVARIAN CANCER

人类乳腺癌和卵巢癌加起来占16.2万新病例 每年的癌症，或者说基本上三分之一的癌症发生在女性。 此外，它们每年造成55000人死亡，或者说基本上是1人死亡 女性癌症相关死亡人数的四分之一。HER-2/neu原癌基因是 一种假定的生长因子受体，与之相关但不同 表皮生长因子受体。在我们实验室所做的研究 结果表明，该基因在约30%的人类中被扩增和/或过度表达 乳腺癌和卵巢癌。此外，此更改与以下内容相关 对于发生肿瘤的患者来说，这是一个糟糕的临床结果。这个 这项提议的目标是调查这一可能的作用 改变在这些疾病的发病机制中起作用。转染法 将进行将人类乳腺和卵巢细胞转化为细胞的研究 HER-2/neu基因的单拷贝和低水平表达 发现具有模拟这种变化的扩增/过表达基因的细胞 在人类乳腺癌和卵巢癌中。它的生物学效应 将对改变进行调查，包括对DNA合成、细胞 裸鼠的生长、细胞侵袭性和致瘤性。在……里面 此外，针对该基因产物胞外区的抗体将 在体外和体内对含有这种改变的细胞进行研究 确定抗体是否改变了由此介导的生物效应 更改。这些研究可能会导致开发新的治疗方法 基于这种癌基因改变的这些疾病的治疗方法。

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.