ROLE OF KERATINOCYTE SUB-POPULATIONS IN TUMOR PROMOTION

我们的实验室有兴趣定义差异贡献 角质形成细胞的特定亚群对乳头状瘤的形成 和癌在暴露于化学物质的单一局部应用后 致癌物，然后反复暴露于12-0-十四烷酰基佛波醇-13- 乙酸盐（TPA）。 我们的假设是TPA不同程度地刺激 皮肤中的角质形成细胞亚群。 这些亚群使 对肿瘤形成的不同贡献。 我们已经确定 表皮细胞的几个不同亚群，包括一个群体 小而致密的细胞只存在于TPA治疗的小鼠中， 其特征在于增强的功能和生物化学反应性。 这 角质形成细胞的亚群产生显著量的反应性 氧中间产物以及炎症因子白细胞介素-1（IL-1） 调解员 一个更小，颗粒更少的角质形成细胞亚群， 在TPA治疗的反应中增殖，并且在肿瘤的后期阶段 启动过程中，具有ODC的高组成型表达。 这 亚群可能含有最终形成乳头状瘤的细胞， 癌 拟议研究的目标是整合潜在的 活性氧中间体和白细胞介素-1各自的作用 由表达ODC的角质形成细胞亚群产生， 乳头状瘤和癌的生长也是由（可能） 不同的角质细胞亚群。 我们开发了新技术 该联合收割机结合了细胞分选技术和北方印迹方法， 允许检测ODC和IF-1的mRNA转录水平， TPA短期和长期治疗后的角质形成细胞亚群 为了更好地了解分子和细胞基础， 促进肿瘤的发展

Our laboratory is interested in defining the differential contribution made by specific subpopulations of keratinocytes to the formation of papillomas and carcinomas after exposure to a single topical application of a chemical carcinogen followed by repeated exposure to 12-0-tetradecanoylphorbol-13- acetate (TPA). Our hypothesis is that TPA differentially stimulates keratinocytes subpopulations in the skin. These subpopulations make distinctly different contributions to tumor formation. We have identified several distinct subpopulations of epidermal cells, including a population of small, dense cells present only in TPA treated mice that is characterized by enhanced functional and biochemical reactivity. This subpopulation of keratinocytes produces significant amounts of reactive oxygen intermediates as well as Interleukin-1 (IL-1), an inflammatory mediator. A smaller, less granular keratinocyte subpopulation rapidly proliferates in response to TPA treatment, and at later stages in the tumor promotion process, has high constitutive expression of ODC. This subpopulation may contain cells that ultimately form papillomas and carcinomas. The goal of the proposed studies is to integrate the potential respective roles of reactive oxygen intermediates and Interleukin-1 produced by subpopulations of keratinocytes with the expression of ODC and the growth of papillomas and carcinomas that also arise from a (possibly) different subpopulation of keratinocytes. We have developed new techniques that combine cell sorting technology and Northern blotting procedures that allow detection of mRNA transcription levels of ODC and IF-1 in specific keratinocyte subpopulations following short and long term TPA treatment in order to gain a better understanding of the molecular and cellular basis for tumor promotion and progression.