ENHANCEMENT OF ONCOGENE EXPRESSION AND MAMMARY CANCER

已在基因组中鉴定出20多个不同的转化基因。 致癌逆转录病毒。这些癌基因中的每一个在 脊椎动物物种的染色体DNA。目前的证据表明 这组高度保守的基因可能在细胞中起着至关重要的作用 增殖和/或分化。此外，不适当的 其中一些基因的表达被认为与糖尿病的发生有关。 癌症。我们的假设是，癌基因表达的放松调控可能是 一种可能的诱发人类肿瘤的一般机制。我们的 人们一直致力于研究ras基因的细胞同源基因， 哈维和柯尔斯滕肉瘤病毒携带的癌基因。在这项研究中 我们正在研究ras基因表达在诱导卵巢癌发生中的作用。 大鼠和人类乳腺癌。在一项对200多个人乳房的研究中 在癌症中，我们观察到c-ras-H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。然而，一个被放大或重排的 C-ras-H基因在人乳腺癌中未检测到。因此， C-ras-H基因在这些肿瘤中表达下调的机制 仍有待确定。C-ras-H增强机制的研究 基因表达，我们将测定c-ras-H在生长和发育过程中的表达 生长受阻的人乳腺癌细胞(MCF-7)，生长与退化 大鼠乳腺肿瘤，激素依赖性肿瘤与激素非依赖性肿瘤，以及 啮齿动物的乳腺在正常发育和化学或化学或 病毒致癌。这项提议的目标是为我们提供一个 更好地理解机制的基本基础 癌基因参与肿瘤的发展和生长。

Over twenty distinct transforming genes have been identified in the genomes of oncogenic retroviruses. Each of these oncogenes has a homologue in the chromosomal 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-ras-H in 70% of estrogen and progesterone receptor positive tumors and 40% of estrogen and progesterone receptor negative tumors. Whereas, an amplified or rearranged c-ras-H gene has not been detected in human mammary carcinomas. Thus, the mechanism by which c-ras-H gene expression is deregulated in these tumors remain to be determined. To study the mechanism of the enhanced c-ras-H gene expression, we will determine the c-ras-H 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.