The Mechanistic Role of Iodine in Breast Carcinogenesis
Final rept. 15 Jul 2004-14 Jul 2005
CALIFORNIA UNIV LOS ANGELES
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There is both considerable interest and ignorance in the possible role of iodine in the etiology and prognosis of breast cancer. This project is the first step in elucidating a mechanistic role for iodine in breast carcinogenesis. The data that we have been able to generate to date suggest that our hypothesis is correct namely, using transgenic human breast cancer cells MCF7 overexpressing the sodiumiodide symporter NIS andor lactoperoxidase LPO, we have shown that NIS facilitates death or survival pathways following irradiation, a known human breast carcinogen, depending on the presence or absence of iodine, respectively, and that this switching can be modulated by the cells ability to organify and stabilize the iodine via LPO. Further, we have shown that expression of both NIS and LPO will radiosensitize the MCF7 cells while NIS alone will make them radioresistant and more aggressive. These data agree with observations made by others demonstrating that iodine deficiency is correlated with increased breast cancer incidence, and that a large percentage of human breast cancers overexpress NIS. Additionally, the fact that NIS and LPO are most active in the mammary glands during late pregnancy and lactation may explain the well established observation that early and frequent parity and long lactation history reduce the risk for breast cancer development. We are confident that the data from the experiments currently in progress should help to strengthen our already existing results. Clarification of these issues should foster future studies not only in breast cancer diagnosis and therapy but also in prevention through conscious changes in diet and environment.
- Anatomy and Physiology