Amphiphysin and Breast Cancer
Final rept. 1 Oct 1997-30 Sep 1999
YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
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Amphiphysin I is a 128 kD nerve terminal protein with a role in clathrin mediated endocytosis, actin function and intracellular signaling. Amphiphysin was first identified as an autoantigen by our laboratory in breast cancer patients with the neurological disease Stiff-man syndrome. We have tested a large case load of patients with neurological disease for autoantibodies by immunocytochemistry and Western blotting. Thirteen patients have tested positive for amphiphysin autoantibodies and cancer. In two cases, the autoantibodies were discovered before the cancer, prompting a search for occult neoplasia. We tested breast tumors for the presence of amphiphysin by RT-PCR and Western blotting. We cloned an alternatively spliced isoform of amphiphysin I from a breast cancer cell line and demonstrated low level expression in several non-neuronal tissues and enhanced expression in several breast cancers. We have also found that amphiphysin interacts with members of the cyclin dependent kinase gene family and may be involved in cell cycle control. Finally, we have produced an amphiphysin knock-out mouse and are currently analyzing the phenotype.
- Medicine and Medical Research