Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer.
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.
Floyd
S
S
Howard Hughes Medical Institute, Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.
Butler
M H
MH
Cremona
O
O
David
C
C
Freyberg
Z
Z
Zhang
X
X
Solimena
M
M
Tokunaga
A
A
Ishizu
H
H
Tsutsui
K
K
De Camilli
P
P
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D005260:Female; D015870:Gene Expression; D006801:Humans; D007536:Isomerism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D009422:Nervous System Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D051381:Rats; D016750:Stiff-Person Syndrome / Q000150:complications / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D009419:Nerve Tissue Proteins; C075637:amphiphysin