ENHANCEMENT OF ONCOGENE EXPRESSION AND MAMMARY CANCER

癌基因表达的增强与乳腺癌

• 批准号: 3939281
• 负责人: Y S CHO-CHUNG
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3939281
• 关键词: Retroviridae disease; breast neoplasms; carcinoma; cell growth regulation; chemical carcinogenesis; developmental genetics; estrogens; gene expression; hormone related neoplasm /cancer; human tissue; mammary gland; mouse sarcoma virus; neoplasm /cancer genetics; neoplasm /cancer remission /regression; neoplastic growth; oncogenes; oncogenic virus; progesterone; regulatory gene; viral carcinogenesis; virus genetics

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.

已经鉴定了20多个转化基因， 致癌逆转录病毒的基因组。 这些致癌基因中的每一个都有 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， 与癌症的发生有关 我们的假设是 癌基因表达的失调可能是一种可能的普遍的 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， 哈维和克尔斯滕肉瘤病毒携带的致癌基因。 在 本研究我们正在研究ras基因表达在 诱导大鼠和人乳腺癌。 在一项研究中 在200多例人类乳腺癌中， c-rasH在70%的雌激素中表达升高， 孕激素受体阳性肿瘤和40%的雌激素， 孕酮受体阴性肿瘤。 然而，放大的或 在人乳腺癌组织中未发现c rasH基因重排 癌 因此，c-rasH基因 在这些肿瘤中表达失调仍有待进一步研究。 测定 探讨c-rasH增强的机制 基因表达，我们将确定c-rasH的表达， 生长和生长停滞的人乳腺癌细胞（MCF-7）， 生长与消退大鼠乳腺肿瘤，乳腺癌依赖性 与非乳腺依赖性肿瘤相比， 正常发育期的啮齿类动物和化学或病毒 致癌作用 这项提案的目的是为我们提供一个 更好地理解机制的根本基础， 哪些癌基因参与肿瘤的发展， 增长