Chromatin Structure and Breast Cancer Radiosensitivity
Final rept. 15 Sep 2002-14 Sep 2007
WASHINGTON UNIV ST LOUIS MO
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The hMOF protein is a chromatin-modifying factor. Chromatin structure plays a critical role in gene expression. Since hMOF has a chromodomain region as well as acetyl transferase activity, its inactivation can influence modification of chromatin during DNA metabolism. The proposed experiments of this grant proposal will determine functions of hMOF gene. This will be achieved by generating isogenic cells with and without hMOF function. Both in vivo and in vitro experiments will be performed to determine the function of hMOF in context with radioresponsiveness and oncogenic transformation. If hMOF proves to be involved in the radioresponsiveness and neoplastic transformation, then the clinical implications of this proposal are highly significant. It may, in the future, be prudent to screen each breast cancer patient prior to any final therapeutic decision. This will be accomplished through the use of quantitative RT-PCR and the test results can be obtained within a day. There are several benefits of identifying an individuals normal tissue with loss of hMOF gene expression. First, it will allow us to prospectively identify the sensitive subset of patients. Second, the radiosensitive patients will be taken for an alternative therapy if it exists and would be spared a great deal of suffering, Third, it will be possible that once we identify a subset of patients that show a genetic basis of radiation sensitivity, the radiation dose to the remaining breast cancer patients could be increased to be more effective for local tumor control. Fourth, ti will provide health professionals a molecular diagnostic approach to predict the suitability of an individual for radiotherapy.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research