DMBA-INDUCED SELF-REGRESSING TUMORS--ROLE OF H-RAS

化学致癌物模型系统的设计已经非常复杂。 有助于促进对肿瘤发生机制的理解。 我们一直在使用多环芳烃DMBA来诱导 兔皮肤肿瘤的形成。一个协议被用来获得一个 一种特殊类型的肿瘤，角化棘皮瘤，即良性和 自我倒退。 这一建议接近了较少研究的良性肿瘤领域。 增加了一个有趣的观点，那就是研究肿瘤的退化 进程。已经完成的工作已经确定激活的H-RAS是 这一系统的重要组成部分，并使用病理学的组合， 分子生物学和免疫组织化学在不同阶段的表达 将对肿瘤系统进行调查。使用聚合酶链式反应扩增和 寡核苷酸杂交肿瘤发展的早期阶段将是 分析了角化棘皮瘤向鳞状细胞的进展 癌症。对人类角化棘皮瘤样本的平行研究将 将它们与动物研究联系起来。美国政府的角色 H-ras癌基因在肿瘤消退过程中的作用将被广泛研究 使用针对突变蛋白的特定抗体的详细信息。至 完成回归过程的分析，维甲酸和转化生长因子β， 将在系统中引入上皮分化试剂以 研究它们与H-ras癌基因表达的相关性。对此的研究 人和兔DMBA诱发的良性肿瘤和自退性肿瘤 模型应提供有关ras癌基因在 肿瘤发生的不同阶段。

The design of model systems of chemical carcinogenes has been extremely useful in advancing the understanding of the mechanisms of tumorigenesis. We have been using the polycyclic aromatic hydrocarbon DMBA to induce in rabbits the formation of skin tumors. A protocol was utilized to obtain a particular type of tumor, keratoacanthoma, that is benign and self-regressing. This proposal approaches the less frequently studied field of benign tumors with the added interesting point of looking into a tumor regression process. Already completed work has identified activated H-ras as an important component of this system and using a combination of pathology, molecular biology and immunohistochemistry the different phases of this tumor system will be investigated. Using PCR amplification and oligonucleotide hybridization the early stages of tumor development will be analyzed as well as the progression from keratoacanthoma to squamous cell carcinoma. Parallel studies with samples from human keratoacanthoma will be undertaken to correlate them with the animal studies. The role of the H-ras oncogene in the process of tumor regression will be studied in great detail making use of specific antibodies for the mutant protein. To complete the analysis of the regression process, retinoids and TGF beta, agents of epithelial differentiation will be introduced in the system to study their correlation with H-ras oncogene expression. The study of this benign and self-regressing tumor in both humans and the rabbit DMBA induced model should provide important information on the role of ras oncogenes in the different stages of tumorigenesis.