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.

尽管有相对较大的信息 逆转录病毒癌基因及其特异性蛋白的分子结构 产品，对它们转化的机制知之甚少 细胞。 此外，原始癌基因，逆转录病毒的细胞对应物 癌基因在正常细胞中已发现，但它们的表达较低，并且 这种低表达的机制尚不清楚。 可以想象 通过显然增加增加肿瘤发育的物质 细胞增殖通过改变定量或时间来做到这一点 细胞癌基因的表达。 了解细胞机制 管理病毒和细胞癌基因的表达 因此提供了有关肿瘤细胞生长机制的洞察力 和肿瘤发育。 有时，肿瘤细胞会区分 自发，然后完全回归。 有人建议营地 可能与肿瘤细胞的形态分化有关 由于用二丁酰营地治疗某些肿瘤细胞，前列腺素E1 营地磷酸二酯酶的抑制剂诱导不可逆的形态学 分化。 这种区别可能是对 恶性肿瘤得到了这样的观察，即当没有产生肿瘤 这些处理过的细胞被接种到动物中。 调查因素 影响转化细胞的表型回归，我们选择了一个 NIH 3T3细胞的细胞系433，其中包含转化的RAS基因 ha-musv侧翼是mmtv的ltr； Ras基因在433个细胞中的表达是 因此由小鼠乳腺肿瘤病毒启动子（MMTV-LTR）控制 受糖皮质激素的控制。 因此，表型正常433 细胞被转化并产生RAS基因产物P21，仅在 糖皮质激素的添加。 我们还使用了NIH 3T3细胞的克隆13-3B-4， HA-MUSV DNA转染剂，其v-rash基因的播种不在 糖皮质激素的控制。 这项研究的目的是调查 细胞内调节因子（例如环状核苷酸）的影响， MMTV-LTR上的激素和生长因子和MOLV-LTR调控 RAS基因的表达。