Skip to main content
Molecular Medicine logoLink to Molecular Medicine
. 1998 Jan;4(1):29–39.

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

S Floyd 1, M H Butler 1, O Cremona 1, C David 1, Z Freyberg 1, X Zhang 1, M Solimena 1, A Tokunaga 1, H Ishizu 1, K Tsutsui 1, P De Camilli 1
PMCID: PMC2230265  PMID: 9513187

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.

Full text

PDF
29

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauer F., Urdaci M., Aigle M., Crouzet M. Alteration of a yeast SH3 protein leads to conditional viability with defects in cytoskeletal and budding patterns. Mol Cell Biol. 1993 Aug;13(8):5070–5084. doi: 10.1128/mcb.13.8.5070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bauerfeind R., Takei K., De Camilli P. Amphiphysin I is associated with coated endocytic intermediates and undergoes stimulation-dependent dephosphorylation in nerve terminals. J Biol Chem. 1997 Dec 5;272(49):30984–30992. doi: 10.1074/jbc.272.49.30984. [DOI] [PubMed] [Google Scholar]
  3. Bogue C. W., Gross I., Vasavada H., Dynia D. W., Wilson C. M., Jacobs H. C. Identification of Hox genes in newborn lung and effects of gestational age and retinoic acid on their expression. Am J Physiol. 1994 Apr;266(4 Pt 1):L448–L454. doi: 10.1152/ajplung.1994.266.4.L448. [DOI] [PubMed] [Google Scholar]
  4. Butler M. H., David C., Ochoa G. C., Freyberg Z., Daniell L., Grabs D., Cremona O., De Camilli P. Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle. J Cell Biol. 1997 Jun 16;137(6):1355–1367. doi: 10.1083/jcb.137.6.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Cremona O., De Camilli P. Synaptic vesicle endocytosis. Curr Opin Neurobiol. 1997 Jun;7(3):323–330. doi: 10.1016/s0959-4388(97)80059-1. [DOI] [PubMed] [Google Scholar]
  7. Crouzet M., Urdaci M., Dulau L., Aigle M. Yeast mutant affected for viability upon nutrient starvation: characterization and cloning of the RVS161 gene. Yeast. 1991 Oct;7(7):727–743. doi: 10.1002/yea.320070708. [DOI] [PubMed] [Google Scholar]
  8. Dalmau J., Graus F., Cheung N. K., Rosenblum M. K., Ho A., Cañete A., Delattre J. Y., Thompson S. J., Posner J. B. Major histocompatibility proteins, anti-Hu antibodies, and paraneoplastic encephalomyelitis in neuroblastoma and small cell lung cancer. Cancer. 1995 Jan 1;75(1):99–109. doi: 10.1002/1097-0142(19950101)75:1<99::aid-cncr2820750117>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  9. Darnell R. B. Onconeural antigens and the paraneoplastic neurologic disorders: at the intersection of cancer, immunity, and the brain. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4529–4536. doi: 10.1073/pnas.93.10.4529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. David C., McPherson P. S., Mundigl O., de Camilli P. A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):331–335. doi: 10.1073/pnas.93.1.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. David C., Solimena M., De Camilli P. Autoimmunity in stiff-Man syndrome with breast cancer is targeted to the C-terminal region of human amphiphysin, a protein similar to the yeast proteins, Rvs167 and Rvs161. FEBS Lett. 1994 Aug 29;351(1):73–79. doi: 10.1016/0014-5793(94)00826-4. [DOI] [PubMed] [Google Scholar]
  12. De Camilli P., Cameron R., Greengard P. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections. J Cell Biol. 1983 May;96(5):1337–1354. doi: 10.1083/jcb.96.5.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. De Camilli P., Thomas A., Cofiell R., Folli F., Lichte B., Piccolo G., Meinck H. M., Austoni M., Fassetta G., Bottazzo G. The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer. J Exp Med. 1993 Dec 1;178(6):2219–2223. doi: 10.1084/jem.178.6.2219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dropcho E. J. Antiamphiphysin antibodies with small-cell lung carcinoma and paraneoplastic encephalomyelitis. Ann Neurol. 1996 May;39(5):659–667. doi: 10.1002/ana.410390516. [DOI] [PubMed] [Google Scholar]
  15. Folli F., Solimena M., Cofiell R., Austoni M., Tallini G., Fassetta G., Bates D., Cartlidge N., Bottazzo G. F., Piccolo G. Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. N Engl J Med. 1993 Feb 25;328(8):546–551. doi: 10.1056/NEJM199302253280805. [DOI] [PubMed] [Google Scholar]
  16. Grabs D., Slepnev V. I., Songyang Z., David C., Lynch M., Cantley L. C., De Camilli P. The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence. J Biol Chem. 1997 May 16;272(20):13419–13425. doi: 10.1074/jbc.272.20.13419. [DOI] [PubMed] [Google Scholar]
  17. Hackett A. J., Smith H. S., Springer E. L., Owens R. B., Nelson-Rees W. A., Riggs J. L., Gardner M. B. Two syngeneic cell lines from human breast tissue: the aneuploid mammary epithelial (Hs578T) and the diploid myoepithelial (Hs578Bst) cell lines. J Natl Cancer Inst. 1977 Jun;58(6):1795–1806. doi: 10.1093/jnci/58.6.1795. [DOI] [PubMed] [Google Scholar]
  18. Jahn R., Schiebler W., Ouimet C., Greengard P. A 38,000-dalton membrane protein (p38) present in synaptic vesicles. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4137–4141. doi: 10.1073/pnas.82.12.4137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kadlec L., Pendergast A. M. The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation. Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12390–12395. doi: 10.1073/pnas.94.23.12390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Leprince C., Romero F., Cussac D., Vayssiere B., Berger R., Tavitian A., Camonis J. H. A new member of the amphiphysin family connecting endocytosis and signal transduction pathways. J Biol Chem. 1997 Jun 13;272(24):15101–15105. doi: 10.1074/jbc.272.24.15101. [DOI] [PubMed] [Google Scholar]
  23. Lichte B., Veh R. W., Meyer H. E., Kilimann M. W. Amphiphysin, a novel protein associated with synaptic vesicles. EMBO J. 1992 Jul;11(7):2521–2530. doi: 10.1002/j.1460-2075.1992.tb05317.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McPherson P. S., Garcia E. P., Slepnev V. I., David C., Zhang X., Grabs D., Sossin W. S., Bauerfeind R., Nemoto Y., De Camilli P. A presynaptic inositol-5-phosphatase. Nature. 1996 Jan 25;379(6563):353–357. doi: 10.1038/379353a0. [DOI] [PubMed] [Google Scholar]
  25. Mundigl O., Ochoa G. C., David C., Slepnev V. I., Kabanov A., De Camilli P. Amphiphysin I antisense oligonucleotides inhibit neurite outgrowth in cultured hippocampal neurons. J Neurosci. 1998 Jan 1;18(1):93–103. doi: 10.1523/JNEUROSCI.18-01-00093.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Munn A. L., Stevenson B. J., Geli M. I., Riezman H. end5, end6, and end7: mutations that cause actin delocalization and block the internalization step of endocytosis in Saccharomyces cerevisiae. Mol Biol Cell. 1995 Dec;6(12):1721–1742. doi: 10.1091/mbc.6.12.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Navone F., Jahn R., Di Gioia G., Stukenbrok H., Greengard P., De Camilli P. Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells. J Cell Biol. 1986 Dec;103(6 Pt 1):2511–2527. doi: 10.1083/jcb.103.6.2511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pawson T. Protein modules and signalling networks. Nature. 1995 Feb 16;373(6515):573–580. doi: 10.1038/373573a0. [DOI] [PubMed] [Google Scholar]
  29. Posner J. B., Dalmau J. O. Paraneoplastic syndromes affecting the central nervous system. Annu Rev Med. 1997;48:157–166. doi: 10.1146/annurev.med.48.1.157. [DOI] [PubMed] [Google Scholar]
  30. Ramjaun A. R., Micheva K. D., Bouchelet I., McPherson P. S. Identification and characterization of a nerve terminal-enriched amphiphysin isoform. J Biol Chem. 1997 Jun 27;272(26):16700–16706. doi: 10.1074/jbc.272.26.16700. [DOI] [PubMed] [Google Scholar]
  31. Sakamuro D., Elliott K. J., Wechsler-Reya R., Prendergast G. C. BIN1 is a novel MYC-interacting protein with features of a tumour suppressor. Nat Genet. 1996 Sep;14(1):69–77. doi: 10.1038/ng0996-69. [DOI] [PubMed] [Google Scholar]
  32. Shupliakov O., Löw P., Grabs D., Gad H., Chen H., David C., Takei K., De Camilli P., Brodin L. Synaptic vesicle endocytosis impaired by disruption of dynamin-SH3 domain interactions. Science. 1997 Apr 11;276(5310):259–263. doi: 10.1126/science.276.5310.259. [DOI] [PubMed] [Google Scholar]
  33. Sivadon P., Bauer F., Aigle M., Crouzet M. Actin cytoskeleton and budding pattern are altered in the yeast rvs161 mutant: the Rvs161 protein shares common domains with the brain protein amphiphysin. Mol Gen Genet. 1995 Feb 20;246(4):485–495. doi: 10.1007/BF00290452. [DOI] [PubMed] [Google Scholar]
  34. Sparks A. B., Hoffman N. G., McConnell S. J., Fowlkes D. M., Kay B. K. Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins. Nat Biotechnol. 1996 Jun;14(6):741–744. doi: 10.1038/nbt0696-741. [DOI] [PubMed] [Google Scholar]
  35. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tsutsui K., Maeda Y., Tsutsui K., Seki S., Tokunaga A. cDNA cloning of a novel amphiphysin isoform and tissue-specific expression of its multiple splice variants. Biochem Biophys Res Commun. 1997 Jul 9;236(1):178–183. doi: 10.1006/bbrc.1997.6927. [DOI] [PubMed] [Google Scholar]
  37. Vieira A. V., Lamaze C., Schmid S. L. Control of EGF receptor signaling by clathrin-mediated endocytosis. Science. 1996 Dec 20;274(5295):2086–2089. doi: 10.1126/science.274.5295.2086. [DOI] [PubMed] [Google Scholar]
  38. Wiedenmann B., Huttner W. B. Synaptophysin and chromogranins/secretogranins--widespread constituents of distinct types of neuroendocrine vesicles and new tools in tumor diagnosis. Virchows Arch B Cell Pathol Incl Mol Pathol. 1989;58(2):95–121. doi: 10.1007/BF02890062. [DOI] [PubMed] [Google Scholar]
  39. Wigge P., Köhler K., Vallis Y., Doyle C. A., Owen D., Hunt S. P., McMahon H. T. Amphiphysin heterodimers: potential role in clathrin-mediated endocytosis. Mol Biol Cell. 1997 Oct;8(10):2003–2015. doi: 10.1091/mbc.8.10.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Williams C. L. Basic science of small cell lung cancer. Chest Surg Clin N Am. 1997 Feb;7(1):1–19. [PubMed] [Google Scholar]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ

RESOURCES