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

化学致癌物的模型系统的设计一直是非常复杂的。 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诱导， 兔皮肤肿瘤的形成。使用一种方案来获得 一种特殊类型的肿瘤，角化棘皮瘤，是良性的， 自我回归 这一建议接近较少研究的良性肿瘤领域 还有一个有趣的观点， 过程 已经完成的工作已经确定激活的H-ras是一种 该系统的重要组成部分，并使用病理学， 分子生物学和免疫组织化学的不同阶段 将研究肿瘤系统。 使用PCR扩增和 寡核苷酸杂交肿瘤发展的早期阶段， 分析以及从角化棘皮瘤到鳞状细胞的进展 carcinoma. 对人类角化棘皮瘤样本的平行研究将 将它们与动物研究相关联。 的作用 H-ras癌基因在肿瘤消退过程中的作用将得到深入研究 使用突变蛋白的特异性抗体的细节。 到 完成回归过程、类维生素A和TGF β的分析， 将在系统中引入上皮分化剂， 研究其与H-ras癌基因表达的相关性。 研究这一 良性和自我消退的肿瘤在人类和兔DMBA诱导 模型应该提供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.