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

Mol Med. 1998 Jan;4(1):29-39.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Antibodies / analysis
  • Antibodies / immunology
  • Antibodies, Monoclonal / immunology
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Autoimmunity
  • Blotting, Western
  • Brain / metabolism
  • Breast / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / metabolism*
  • Chromatography, Affinity
  • Cloning, Molecular
  • Female
  • Gene Expression
  • Humans
  • Isomerism
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism*
  • Nervous System Diseases / complications
  • Nervous System Diseases / genetics
  • Nervous System Diseases / immunology
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Rats
  • Stiff-Person Syndrome / complications
  • Stiff-Person Syndrome / genetics
  • Stiff-Person Syndrome / immunology
  • Tumor Cells, Cultured

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Autoantigens
  • Nerve Tissue Proteins
  • amphiphysin