NEOPLASTIC HEMATOPOIETIC CELL GROWTH--INTERACTIONS WITH RETROVIRUSES

肿瘤造血细胞生长——与逆转录病毒的相互作用

• 批准号: 3963338
• 负责人: F W RUSCETTI
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 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/3963338
• 关键词: Herpesvirus saimiri; T lymphocyte; cell growth regulation; clone cells; flow cytometry; genetic transcription; glucocorticoids; hematopoiesis; hormone regulation /control mechanism; human T cell lymphotropic virus type 2; human tissue; immune adherence reaction; immunofluorescence technique; interleukin 2; leukocyte activation /transformation; mixed tissue /cell culture; monoclonal antibody; neoplasm /cancer immunology; neoplastic cell; neoplastic growth; oncogenes; phosphatidylinositols; protein kinase C; radiotracer; transforming virus; viral carcinogenesis

Binding of the regulatory peptide, interleukin 2 (IL 2) to its specific receptor is a prerequisite for activated T-lymphocytes to grow. Recombinant purified IL 2 has been used to identify post-receptor events important in mediating IL 2 function. (Ca++) mobilization, protein kinase C activation and phosphoinositol hydrolysis has all been found to correlate with IL 2 induced gene activation. The genes activated by IL 2 have included those for the IL 2 receptor, gamma interferon and the proto-oncogenes, c-fos, c-myb and c-myc. IL 2 stimulation of IL 2 receptor gene transcription results in an increase of receptors on the cell surface of low affinity for IL 2. Further studies of IL 2 receptor distribution has shown it also to be expressed on immature thymocytes, monocytes/macrophages, mast cells and a variety of hematopoietic progenitor cells. In these cells, the IL 2 receptor gene is under the transscriptional control of hematopoietic growth factors such as interleukin-3 and granulocyte/macrophage colony stimulating factor. Studies were conducted concerning the mechanism of myeloid cell differentiation. Variants of the murine myelomonocytic leukemia cell line such as WEHI-3B D+ which can be induced to differentiate into monocyte/macrophages and the WEHI-3B D- is unresponsive to these inducers were developed. The unresponsive cell line was induced to differentiate to granulocytes as well as monocytes by 1,25 dihydroxy-cholcalciferol (1,25 (OH)2 D3), the biologically active metabolite of Vitamin D3. The differentiation of both cell types was accompanied by cessation of cellular growth accompanies changes in morphologic and cytochemical properties of the cells. This suggests that leukemic cells unresponsive to differentiation agents acting at the cell surface retain their ability to differentiate in response to agents that do not act via the plasma membrane such as 1,25 (OH)2 D3 which has cytosolic/nuclear receptors. Regulation of proto-oncogene transcription was also studied in these cell lines. Expression of c-fos, c-myc and c-myb was identical in the subclones whether the cells differentiated or not suggesting that expression of these genes was not sufficient to induce differentiation.

调节肽--白介素2与其特异性结合 受体是激活的T淋巴细胞生长的先决条件。 重组纯化的IL-2已用于鉴定受体后事件 在调节IL-2功能中起重要作用。(Ca++)动员，蛋白激酶 C的激活和磷酸肌醇的水解都被发现是相关的。 IL-2诱导的基因激活。IL-2激活的基因有 包括IL-2受体、γ-干扰素和 原癌基因c-fos、c-myb和c-myc。IL-2对IL-2受体的刺激作用 基因转录导致细胞表面受体增加 对IL-2的低亲和力。IL-2受体分布的进一步研究 研究表明，它也表达在未成熟的胸腺细胞上， 单核/巨噬细胞、肥大细胞和多种造血祖细胞 细胞。在这些细胞中，IL-2受体基因处于 造血生长因子的转录调控 白细胞介素3和粒细胞/巨噬细胞集落刺激因子。 对髓系细胞的机制进行了研究。 差异化。小鼠粒单核细胞白血病细胞系的变异 如WEHI-3B D+，可诱导分化为 单核/巨噬细胞和WEHI-3B D-对这些诱导剂无反应 都被开发出来了。无反应的细胞系被诱导分化为 1，25-二羟基胆钙化醇(1，25)对粒细胞和单核细胞的作用 (OH)2D3)，维生素D3的生物活性代谢物。这个 两种细胞类型的分化都伴随着细胞的停止。 生长伴随着细胞形态和细胞化学性质的变化 这些细胞。这表明白血病细胞对 作用于细胞表面的分化剂保持了它们的能力 对不通过质膜起作用的药物作出反应而区别对待 如具有胞液/核受体的1，25(OH)2D3。规管 原癌基因转录也在这些细胞系中进行了研究。 C-fos、c-myc和c-myb在亚克隆中的表达是否相同 细胞分化与否表明这些基因的表达 不足以诱导分化。