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Chromatin Structure and Breast Cancer Radiosensitivity

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Annual rept. 15 Sep 2004-14 Sep 2005

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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 radio responsiveness and oncogenic transformation. If hMOF proves to be involved in the radio responsiveness 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 betaken for an alternative therapy if exist 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 patients could be increased to be more effective for local tumor control. Fourth it will provide health professionals a molecular diagnostic approach to predict the suitability of an individual for radiotherapy.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

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