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Expression of Amphiphysin I, an Autoantigen of Paraneoplastic Neurological Syndromes, in Breast Cancer

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Abstract

Amphiphysin I is a 128 kD protein highly concentrated in nerve terminals, where it has a putative role in endocytosis. It is a dominant autoantigen in patients with stiff-man syndrome associated with breast cancer, as well as in other paraneoplastic autoimmune neurological disorders. To elucidate the connection between amphiphysin I autoimmunity and cancer, we investigated its expression in breast cancer tissue. We report that amphiphysin I was expressed as two isoforms of 128 and 108 kD in the breast cancer of a patient with anti-amphiphysin I antibodies and paraneoplastic sensory neuronopathy. Amphiphysin I was also detectable at variable levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a variety of other non-neuronal tissues. The predominant amphiphysin I isoform expressed outside the brain in humans is the 108 kD isoform which represents an alternatively spliced variant of neuronal amphiphysin I missing a 42 amino acid insert. Our study suggests a link between amphiphysin I expression in cancer and amphiphysin I autoimmunity. The enhanced expression of amphiphysin I in some forms of cancer supports the hypothesis that amphiphysin family members may play a role in the biology of cancer cells.

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Acknowledgments

We thank D. Stern (Yale), A. Perkins (Yale), and K. Tsutsui (Okayama, Japan) for discussion and J. Honnorat (Lyon, France), J. C. Antoine (Saint-Etienne, France), P. Sillevis-Smitt (Rotterdam, The Netherlands), K. Schmierer (Berlin, Germany), and J. Dalmau (New York) for discussing their patients with us. We thank L. Gutierez and C. Howe (Yale) and C. R. Wenger (University of Texas Health Science Center at San Antonio) for help in obtaining human tissues. Some of the material used for this study was provided through the Yale Critical Technologies Service (Dr. C. Howe, Director), and through the National Breast Cancer Tissue Resource of the San Antonio SPORE (Specialized Program of Research Excellence). This work was supported in part by grants from the Human Frontier Science Program and NIH (CA46128 and NS36251) to P. D. C., by fellowships from Telethon and the Human Frontier Science Program to O. C., by a fellowship from the United States Army Medical Research and Development Command to C. D., by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan to K. T., and by NIH grant (P50 CA58183) to the National Breast Cancer Tissue Resource of the San Antonio SPORE.

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Authors and Affiliations

  1. Department of Cell Biology, Howard Hughes Medical Institute, 295 Congress Ave., New Haven, Connecticut, 06510, USA

    Scott Floyd, Margaret Husta Butler, Ottavio Cremona, Carol David, Zachary Freyberg, Xiaomei Zhang &  Pietro De Camilli

  2. Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA

    Michele Solimena

  3. Third Department of Anatomy, Okayama University Medical School, Okayama, Japan

    Akira Tokunaga & Kimiko Tsutsui

  4. Department of Neuropsychiatry, Okayama University Medical School, Okayama, Japan

    Hideki Ishizu

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  1. Scott Floyd
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Correspondence to Pietro De Camilli.

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Communicated by V. T. Marchesi.

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Floyd, S., Butler, M.H., Cremona, O. et al. Expression of Amphiphysin I, an Autoantigen of Paraneoplastic Neurological Syndromes, in Breast Cancer. Mol Med 4, 29–39 (1998). https://doi.org/10.1007/BF03401727

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