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Do Perturbed Epithelial-Mesenchymal Interactions Drive Early Stages of Carcinogenesis?

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Annual rept. 1 Apr 2002-31 Mar 2003

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This application should be considered in the context of the competing theories of carcinogenesis. The first is the somatic mutation theory which is based on two main premises the first, claims that the default state of cells in metazoa is quiescence, and the second posits that cancer is the result of the multistage process where successive mutations accumulate in a single target cell. Much was learned about genes expression under a variety of conditions. However, this aggressive effort failed to provide either an explanation for carcinogenesis or a rationale for effective therapies. The second theory is the tissue organization field theory of carcinogenesis. This theory has adopted two basic premises the first postulates that proliferation is the default state of all cells prokaryotes to metazoa, and the second states that tissues stroma or epithelium, or both are the targets of carcinogens. The first aim tests whether the primary target of the carcinogenic agent nitrosometylurea is the epithelium, the stroma or both. Recombinants will be made where vehicle-treated stromal cells are recombined with epithelial cells from vehicle-treated and carcinogen-treated animals, and stromal cells from carcinogen-treated mammary fat pads are recombined with epithelial cells from vehicle-treated and carcinogen-treated animals. The second aim assesses histoarchitecture changes in the mammary gland in the tissue recombinants developed in Aim 1. Finally, the third aim documents molecular changes in epithelial and stromal pericellular matrices.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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