CHEMICAL TRANSFORMATION OFMOUSE EPIDERMAL KERATINOCYTES

小鼠表皮角质细胞的化学转化

• 批准号: 3178766
• 负责人: Bernard E. Weissman
• 金额: $ 9.7万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3178766
• 关键词: athymic mouse; autoradiography; benzopyrenes; calcium channel blockers; cell differentiation; cell growth regulation; cell population study; chemical carcinogen; chemical carcinogenesis; dosage; electron microscopy; enzyme mechanism; epidermal growth factor; gel filtration chromatography; gene expression; genetic markers; immunofluorescence technique; keratinocyte; methylcholanthrene; radiotracer; tissue /cell culture; tritium

Studies on chemical transformation in vitro have been based primarily on fibroblastic cells. While these results have led to insights into the processes of neoplastic transformation, the majority of human cancers are derived from cells of epithelial origin. Many investigators have attempted to develop a transformation assay based on epithelial cells. Although some systems have proved to be relatively successful for assaying chemical carcinogens, a reproducible assay based on a well-characterized epithelial cell line does not yet exist. Recently, an epidermal keratinocyte cell line of murine origin (Balb/MK) has been developed which possesses stable genetic properties useful for transformation studies. Balb/MK cells have an absolute requirement for epidermal growth factor (EGF) for their continued proliferation. They also will undergo terminal differentiation when exposed to high levels of extracellular calcium. Previous studies have shown that infection of these cells by a variety of mammalian retroviruses leads to an abrogation of the EGF requirement as well as a block in the calcium-induced terminal differentiation pathway. Thus, these cells are potentially useful as a general model for epithelial cell transformation. Initial studies have shown that the treatment of Balb/MK cells with the chemical carcinogen 20'-methylcholanthrene (MCA) leads to the isolation of EGF-independent cell lines in a dose-dependent manner. In addition, these chemically treated cells are also blocked in their ability to respond to calcium-induced terminal differentiation. Therefore, it is proposed that the Balb/MK cell line can be used as the basis for a chemical transformation assay for epithelial cells. The validity of the system will be examined by comparing the effects of known chemical carcinogens in vivo with their effects on the Balb/MK cells. The growth properties of the chemically transformed Balb/MK cells will be characterized by known in vitro parameters as well as assays for tumorigenic potential. The effects of carcinogen treatment on the differentiation phenotype of these cells will be examined by the use of known markers of epidermal differentiation. Finally, the interaction between viral and chemical transformation of these cells will be assessed.

体外化学转化的研究主要基于 成纤维细胞。 尽管这些结果导致了人们对 肿瘤转化的过程，大多数人类癌症是 源自上皮来源的细胞。 许多调查人员试图 开发基于上皮细胞的转化测定。 虽然有些 事实证明，系统对于分析化学物质相对成功 致癌物，一种基于特征良好的上皮的可再现测定法 细胞系还不存在。 最近，鼠起源（BALB/MK）的表皮角质形成细胞系 已经开发了具有稳定的遗传特性的 转型研究。 BALB/MK细胞具有绝对要求 表皮生长因子（EGF）持续增殖。 他们也是 暴露于高水平时，将经历终端分化 细胞外钙。 先前的研究表明，这些感染 细胞通过多种哺乳动物逆转录病毒导致废除 EGF的需求以及钙诱导的终端中的块 分化途径。 因此，这些细胞有可能作为一个 上皮细胞转化的一般模型。 初步研究表明，用BALB/MK细胞处理 化学致癌20'-甲基胆碱（MCA）导致隔离 以剂量依赖性方式独立于EGF的细胞系。 另外，这些 化学处理的细胞的反应能力也被阻止 钙诱导的末端分化。 因此，有人提出 BALB/MK细胞系可用作化学物质的基础 上皮细胞的转化测定法。 系统的有效性将 通过比较已知的化学致癌物在体内的影响来检查 它们对BALB/MK细胞的影响。 生长特性 化学转化的BALB/MK细胞将以已知 体外参数以及肿瘤潜能的测定。 效果 这些细胞的分化表型的致癌物处理 将通过使用已知的表皮分化标记来检查。 最后，这些病毒和化学转化之间的相互作用 将评估细胞。

项目成果

Identification of two 36-kD phosphoproteins associated with altered differentiation in retrovirus-transformed Balb/MK-2 mouse keratinocytes.

鉴定与逆转录病毒转化的 Balb/MK-2 小鼠角质形成细胞分化改变相关的两种 36-kD 磷蛋白。

• DOI: 10.1159/000163682
• 发表时间: 1991
• 期刊: Pathobiology : journal of immunopathology, molecular and cellular biology
• 作者: Makino,JK;Weissman,BE
• 通讯作者: Weissman,BE

Interactions of growth factors and retroviral oncogenes with mitogenic signal transduction pathways of Balb/MK keratinocytes.

生长因子和逆转录病毒癌基因与 Balb/MK 角质形成细胞有丝分裂信号转导途径的相互作用。

• 发表时间: 1988
• 期刊: Oncogene
• 影响因子: 8
• 作者: Falco,JP;Taylor,WG;DiFiore,PP;Weissman,BE;Aaronson,SA
• 通讯作者: Aaronson,SA