ENHANCEMENT OF ONCOGENE EXPRESSION AND MAMMARY CANCER

目前已鉴定出20多个转化基因 致癌逆转录病毒基因组。这些癌基因中的每个都有 一种脊椎动物染色体DNA中的同源物。 目前的证据表明，这组高度保守的基因 可能在细胞增殖和/或分化中起重要作用。 此外，其中一些基因的不适当表达已经 与癌症的发生有牵连。我们的假设是 解除对癌基因表达的管制可能是一种可能的普遍做法 诱导人类肿瘤形成的机制。我们的努力 已经集中在ras基因的细胞同源物上， 哈维和柯尔斯滕肉瘤病毒携带的癌基因。在……里面 本研究旨在探讨ras基因表达在肿瘤发生发展中的作用。 大鼠和人乳腺癌的诱发。在一项研究中 在200多种人类乳腺癌中，我们观察到 C-rash在70%的雌激素和 孕激素受体阳性的肿瘤和40%的雌激素和 孕激素受体阴性肿瘤。鉴于，放大的或 在人类乳腺中未检测到重排的c-rash基因 癌症。因此，c-rash基因 在这些肿瘤中的表达被解除调控仍有待于 下定决心。探讨c-皮疹加重的机制 基因表达，我们将确定c-rash在 生长和生长受阻的人乳腺癌细胞(MCF-7)， 荷尔蒙依赖的大鼠乳腺肿瘤生长与消退 VS激素非依赖性肿瘤，以及 啮齿动物在正常发育和化学或病毒期间 致癌。这项提议的目标是为我们提供一个 更好地理解这些机制的基本基础 哪些癌基因参与了肿瘤的发展和 成长。

Over twenty transforming genes have been identified in the genomes of oncogenic retroviruses. Each of these oncogenes has a homologue in the chrosomal DNA of a vertebrate species. Current evidence indicates that this highly conserved set of genes may play a vital role in cell proliferation and/or differentiation. In addition, inappropriate expression of some of these genes has been implicated in the genesis of cancer. Our hypothesis is that deregulation of oncogene expression may be a possible general mechanism for the induction of neoplasia in humans. Our efforts have been concentrated on the cellular homologue of the ras gene, the oncogene carried by Harvey and Kirsten Sarcoma viruses. In this study we are investigating the role of ras gene expression in the induction of rat and human mammary carcinomas. In a study of more than 200 human breast carcinomas, we have observed elevated expression of c-rasH in 70% of estrogen and progesterone receptor positive tumors and 40% of estrogen and progesterone receptor negative tumors. Whereas, an amplified or rearranged c rasH gene has not been detected in human mammary carcinomas. Thus, the mechanism by which c-rasH gene expression is deregulated in these tumors remain to be determined. To study the mechanism of the enhanced c-rasH gene expression, we will determine the c-rasH expression in growing and growth-arrested human breast cancer cells (MCF-7), growing vs regressing rat mammary tumors, hormone-dependent vs hormone-independent tumors, and the mammary gland of rodents during normal development and chemical or viral carcinogenesis. The goal of this proposal is to provide us a fundamental basis for better understanding the mechanisms by which oncogenes involved in the neoplastic development and growth.