THE REGULATORY MECHANISM OF ONCOGENE EXPRESSION

癌基因表达的调控机制

• 批准号: 4691824
• 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/4691824
• 关键词: cellular oncology; cyclic AMP; gene expression; glucocorticoids; hormone regulation /control mechanism; molecular oncology; mouse mammary tumor virus; neoplasm /cancer genetics; neoplasm /cancer remission /regression; neoplastic growth; oncogenes; prostaglandin E; prostaglandin inhibitors; transforming virus; viral leukemogenesis; virus genetics

In spite of the relatively large body of information concerning the molecular structure of retrovirus oncogenes and their specific protein products, little is known about the mechanisms by which they transform cells. Moreover, proto-oncogenes, the cellular counterpart of retroviral oncogenes, have been found in normal cells but their expression is low and the mechanism for this low expression is not known. It is conceivable that substances that increase tumor development by apparently increasing cellular proliferation do so by altering the quantitative or temporal expression of cellular oncogenes. Understanding the cellular mechanisms governing the expression of both viral and cellular oncogenes would therefore provide an insight into the mechanism of neoplastic cell growth and tumor development. Occasionally, tumor cells differentiate spontaneously and then regress completely. It has been suggested that cAMP may be linked with the morphological differentiation of neoplastic cells since treatment of some tumor cells with dibutyryl cAMP, prostaglandin E1 and inhibitors of cAMP-phosphodiesterase induces irreversible morphological differentiation. That this differentiation may be a reversion of malignancy is supported by the observation that no tumor is produced when these treated cells are inoculated into animals. To investigate factors that affect phenotypic reversion of transformed cells, we have chosen a cell line 433 of NIH 3T3 cells containing the transforming ras gene of Ha-MuSV flanked by LTR of MMTV; the expression of ras gene in 433 cells is therefore controlled by mouse mammary tumor virus promoter (MMTV-LTR) which is under control of glucocorticoid. Thus, the phenotypically normal 433 cells become transformed and produce the ras gene product, p21, only upon addition of glucocorticoid. We also used clone 13-3B-4 of NIH 3T3 cells, the Ha-MuSV DNA transfectant, whose epxression of v-rasH gene is not under control of glucocorticoid. The goal of this study is to investigate the effect of intracellular regulatory factors, such as, cyclic nucleotides, hormones, and growth factors on the MMTV-LTR, and MoLV-LTR regulated expression of ras gene.

尽管有相当多的资料， 逆转录病毒癌基因及其特异蛋白的分子结构 产品，很少有人知道的机制，他们转换 细胞 此外，原癌基因，逆转录病毒的细胞对应物， 在正常细胞中发现了癌基因，但它们的表达很低， 这种低表达的机制尚不清楚。 可以想象 增加肿瘤发展的物质， 细胞增殖是通过改变细胞的数量或时间来实现的。 细胞癌基因的表达。 了解细胞机制 控制病毒和细胞癌基因的表达， 因此，提供了一个深入了解肿瘤细胞生长的机制， 和肿瘤的发展。 偶尔，肿瘤细胞分化 然后完全退化。 有人认为cAMP 可能与肿瘤细胞的形态分化有关 由于用二丁酰cAMP、前列腺素E1 和cAMP-磷酸二酯酶抑制剂诱导不可逆的形态学 分化 这种分化可能是 恶性肿瘤的支持是观察到没有肿瘤产生时， 将这些处理过的细胞接种到动物体内。 调查因素 影响转化细胞的表型逆转，我们选择了 转化ras基因的NIH 3 T3细胞系433 Ha-MuSV两侧为MMTV的LTR; ras基因在433细胞中的表达为 因此受小鼠乳腺肿瘤病毒启动子（MMTV-LTR）控制， 都在糖皮质激素的控制下 因此，表型正常的433 细胞转化并产生ras基因产物p21，只有在 添加糖皮质激素。 我们还使用NIH 3 T3细胞的克隆13-3B-4， Ha-MuSV DNA转染子，其v-rasH基因表达不受抑制， 糖皮质激素的控制。 本研究的目的是调查 细胞内调节因子，如环核苷酸， 激素和生长因子对MMTV-LTR和MoLV-LTR的调节 ras基因的表达。