Breast Tumor Immunity in the Paraneoplastic Neurologic Disorders.
Annual rept. 1 Oct 94-30 Sep 95,
ROCKEFELLER UNIV NEW YORK
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Paraneoplastic neurologic disease PND antigens are proteins normally expressed specifically in neurons that are expressed ectopically in tumors. It is believed that when expressed in tumors outside of the immunologically privilege nervous system, PND antigens stimulate the development of anti-tumor immunity, but also stimulate an autoimmune neuronal degeneration. We are studying PNDs associated with breast cancer and immunity to the Nova and cdr2 antigens, assaying PND expression in clinical breast tumor specimens, and establishing animal models for the disorders. A prerequisite to studying the abnormal expression of PND antigens is an understanding of their normal expression. We have found that the Ndva gene and antigen is normally restricted in expression to neurons. Strikingly, we have discovered that the cdr2 gen is widely expressed, but that its mRNA is under tight translational control, so that the cdr2 antigen is normally made only in neurons and immune privileged testes. This observation provides a novel insight to the biologydf breast tumors, suggesting that they may dysregulate translational control to express abnormal proteins, and alters our approach to the analysis of cdr2 expression in vivo. We have also made significant progress in generating gene constructs to generate mouse models of PND.
- Medicine and Medical Research
- Anatomy and Physiology