Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer.

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.

• Authors: S Floyd, M H Butler, O Cremona, C David, Z Freyberg, X Zhang, M Solimena, A Tokunaga, H Ishizu, K Tsutsui, P De Camilli
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) Vol. 4 Issue 1 Pg. 29-39 (Jan 1998) ISSN: 1076-1551 [Print] England
• PMID: 9513187 (Publication Type: Journal Article, 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.)

Chemical References

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

Topics

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