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Exploiting for Breast Cancer Control a Proposed Unified Mechanism for Reduction of Human Breast Cancer Risk by the Hormones of Pregnancy

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Annual rept. 5 Apr 2005-4 Apr 2006

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In Year 1 we showed that administration of pregnancy-associated hormones to carcinogen-exposed rats not only reduced the appearance of mammary cancers as does pregnancy but also led to generation of AFP in serum at near pregnancy levels in support of our hypothesis. The Year 2 plan was designed to confirm that AFP not the hormones of pregnancy is the proximal inhibitor of breast cancer. We planned to perform similar studies in rodents that would be passively immunized against AFP in which inhibition should fail. However due to the cost of those experiments we first employed an in vitro pseudo-human model for passive immunization. We challenged cultures of HepG2 human liver cancer cells with hormones of pregnancy and demonstrated elevated secretion of AFP into the culture media. When these media were added to cultures of T47D human breast cancer cells cell proliferation was inhibited. However preventing inhibition by adding anti-AFP antibodies was not achieved failing with three different antibodies. Investigation disclosed that the antibodies employed failed to deplete the AFP content of the media. We are now investigating a large panel of antibodies as well as their use in higher concentrations before beginning studies using the in vivo model. Achievement of a strategy that effectively neutralizes AFP is critical to completing the work that was proposed to evaluate whether AFP is the proximal breast cancer inhibitor elicited by the hormones of pregnancy.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

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