Genetics of skin tumor promotion.

Q4 Biochemistry, Genetics and Molecular Biology
J M Angel, J DiGiovanni
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引用次数: 39

Abstract

Cancer development is a multistep process that involves both the activation of protooncogenes and the inactivation of tumor suppressor genes. Furthermore, both epidemiological and experimental data indicate that a third class of genes, tumor susceptibility genes, control the propensity to develop carcinogen-induced tumors. Recent studies suggest that tumor susceptibility is determined by the combined effect of both sensitivity and resistance genes. The mouse skin model of multistage carcinogenesis is an excellent paradigm in which to study the genetics of cancer susceptibility. This is particularly true with regard to tumor promotion, a process that occurs in other organs and species including humans. We have studied the genetics of tumor promotion susceptibility in the mouse two-stage skin tumor model using crosses between sensitive DBA/2 or C3H and resistant C57BL/6 mice. Our results suggest that TPA promotion susceptibility is a multigenic trait. We have tentatively mapped one tumor susceptibility locus, Psl1, to mouse chromosome 9 and are currently identifying and characterizing candidate tumor susceptibility genes that map to this chromosomal region. The multistage model of carcinogenesis in mouse skin has, for more than 50 years, provided a conceptual framework from which to study the carcinogenesis process. Many concepts now currently applied to other tissues and model systems were originally derived from the mouse skin model. Because tumor promotion is an important component of carcinogenesis in humans, the identification of genes that modify response to tumor-promoting stimuli would be a significant advancement in our understanding of the genetic basis of susceptibility to cancer.

促进皮肤肿瘤的遗传学。
癌症的发展是一个多步骤的过程,包括原癌基因的激活和肿瘤抑制基因的失活。此外,流行病学和实验数据都表明,第三类基因,即肿瘤易感基因,控制着致癌诱导肿瘤的发生倾向。近年来的研究表明,肿瘤易感性是由敏感基因和耐药基因共同作用决定的。小鼠皮肤多阶段癌变模型是研究癌变易感性遗传学的一个很好的范例。在肿瘤促进方面尤其如此,这一过程发生在包括人类在内的其他器官和物种中。我们利用敏感的DBA/2或C3H与耐药的C57BL/6小鼠杂交,研究了小鼠两期皮肤肿瘤模型中肿瘤促进易感性的遗传学。我们的结果表明,TPA促进易感性是一种多基因性状。我们已经初步将一个肿瘤易感位点Psl1定位到小鼠9号染色体上,目前正在鉴定和表征该染色体区域的候选肿瘤易感基因。50多年来,小鼠皮肤癌变的多阶段模型为研究癌变过程提供了一个概念框架。目前应用于其他组织和模型系统的许多概念最初都来源于小鼠皮肤模型。由于肿瘤促进是人类癌变的一个重要组成部分,因此确定对肿瘤促进刺激反应进行修饰的基因将是我们对癌症易感性遗传基础理解的重大进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Progress in Tumor Research
Progress in Tumor Research 医学-肿瘤学
CiteScore
2.50
自引率
0.00%
发文量
0
期刊介绍: The scientific book series ''Progress in Tumor Research'' aims to provide in depth information about important developments in cancer research. The individual volumes are authored and edited by experts to provide detailed coverage of topics selected as either representing controversial issues or belonging to areas where the speed of developments necessitates the kind of assistance offered by integrative, critical reviews.
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