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SENCAR Mouse-Skin Tumorigenesis Model

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Tumor Models in Cancer Research

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Over the past few decades, the mouse has been established as the primary organism used to investigate the fundamental mechanisms of skin carcinogenesis and to model human neoplasia. Skin is the most important protective barrier against the harmful and lethal carcinogenic effects of physical (e.g., ultraviolet (UV) radiation), chemical (e.g., polycyclic aromatic hydrocarbons (PAHs)), and biological (e.g., oncogenic viruses) environmental factors. Carcinogenesis has been demonstrated by experimental and epidemiologic studies to be a multifactorial, multigenic, and multiphasic process composed of three major sequential stages: initiation, promotion, and progression (1). A single exposure of a carcinogenic agent such as 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene B(a)P to epidermal cells may result in a small subset of initiating cells carrying irreversible mutations in critical gene(s) such as proto-oncogenes and tumor-suppressor genes, which control normal cellular growth and differentiation (2). In the promotion stage, repeated applications of promoters such as phorbol esters that are generally nonmutagenic bring about many important epigenetic alterations in initiated cells, facilitating the clonal expansion of an initiated phenotype and leading to the formation of benign tumors or papillomas. The early stage of promotion is reversible, but promotion in late stage and progression represents the irreversible phases of carcinogenesis process (3). In progression stage, papillomas acquire additional aberrant genetic and epigenetic changes, and develop into a rapidly growing invasive lesion known as carcinoma. Because of an increasing trend in the incidence of human skin cancer, many laboratories have been involved in the process of developing a suitable skin carcinogenesis model to investigate and understand the tumorigenic factors and the cellular, biochemical, and molecular mechanisms involved in the process of human skin tumorigenesis.

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Authors
  1. Rana P. Singh PhD
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  2. Rajesh Agarwal PhD
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Editors and Affiliations

  1. Lilly Research Laboratories, Indianapolis, IN, USA

    Beverly A. Teicher

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Singh, R.P., Agarwal, R. (2002). SENCAR Mouse-Skin Tumorigenesis Model. In: Teicher, B.A. (eds) Tumor Models in Cancer Research. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-100-8_20

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  • DOI: https://doi.org/10.1007/978-1-59259-100-8_20

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-6883-1

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