ROLE OF KERATINOCYTE SUB-POPULATIONS IN TUMOR PROMOTION

我们的实验室对定义差额贡献感兴趣 角质形成细胞亚群在乳头状瘤形成中的作用 以及暴露于一种化学物质的单一局部应用后的癌症 致癌物质，然后重复暴露于12-0-十四酰佛波醇-13- 醋酸酯(TPA)。我们的假设是TPA会有不同的刺激作用 皮肤中的角质形成细胞亚群。这些亚群使 在肿瘤形成中的作用截然不同。我们已经确定了 几个不同的表皮细胞亚群，包括一个种群 仅在TPA处理的小鼠中存在的小而密集的细胞 以增强的功能和生化反应为特征。这 角质形成细胞亚群产生大量的反应性 氧中间体和白介素1(IL-1)，一种炎性物质 调解人。较小、颗粒较少的角质形成细胞亚群迅速 在TPA治疗后增殖，并在肿瘤的后期阶段 推广过程中，具有较高的ODC结构性表达。这 亚群可能包含最终形成乳头状瘤和 癌症。拟议研究的目标是整合潜在的 活性氧中间体与白介素1各自的作用 由表达ODC和ODC的角质形成细胞亚群产生 乳头状瘤和癌的生长也可能是由 不同亚群的角质形成细胞。我们开发了新技术 结合了细胞分选技术和Northern blotting程序， 允许检测ODC和IF-1在特定细胞中的转录水平 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 用于肿瘤的促进和进展。

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.