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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Dec;82(23):7924–7928. doi: 10.1073/pnas.82.23.7924

Anti-peptide antibodies detect oncogene-related proteins in urine.

H L Niman, A M Thompson, A Yu, M Markman, J J Willems, K R Herwig, N A Habib, C B Wood, R A Houghten, R A Lerner
PMCID: PMC390882  PMID: 3906653

Abstract

Antisera to a number of synthetic peptides predicted from nucleic acid sequences of oncogenes have been used to screen 483 urine samples of cancer patients, pregnant women, and normal controls for the presence of immunologically related proteins. Increased levels of oncogene-related proteins are found during neoplasia and pregnancy. The differential detection of these oncogene-related proteins indicates that panels of monoclonal antibodies may provide a convenient noninvasive means of detecting, classifying, and staging a wide variety of malignancies and may be useful in following fetal development during pregnancy.

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Selected References

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  1. Antoniades H. N., Hunkapiller M. W. Human platelet-derived growth factor (PDGF): amino-terminal amino acid sequence. Science. 1983 May 27;220(4600):963–965. doi: 10.1126/science.6844921. [DOI] [PubMed] [Google Scholar]
  2. Bowen-Pope D. F., Vogel A., Ross R. Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2396–2400. doi: 10.1073/pnas.81.8.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campisi J., Gray H. E., Pardee A. B., Dean M., Sonenshein G. E. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell. 1984 Feb;36(2):241–247. doi: 10.1016/0092-8674(84)90217-4. [DOI] [PubMed] [Google Scholar]
  4. Capon D. J., Chen E. Y., Levinson A. D., Seeburg P. H., Goeddel D. V. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33–37. doi: 10.1038/302033a0. [DOI] [PubMed] [Google Scholar]
  5. Capon D. J., Seeburg P. H., McGrath J. P., Hayflick J. S., Edman U., Levinson A. D., Goeddel D. V. Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations. Nature. 1983 Aug 11;304(5926):507–513. doi: 10.1038/304507a0. [DOI] [PubMed] [Google Scholar]
  6. Der C. J., Cooper G. M. Altered gene products are associated with activation of cellular rasK genes in human lung and colon carcinomas. Cell. 1983 Jan;32(1):201–208. doi: 10.1016/0092-8674(83)90510-x. [DOI] [PubMed] [Google Scholar]
  7. Devare S. G., Reddy E. P., Law J. D., Robbins K. C., Aaronson S. A. Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transforming gene product p28sis. Proc Natl Acad Sci U S A. 1983 Feb;80(3):731–735. doi: 10.1073/pnas.80.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dhar R., Ellis R. W., Shih T. Y., Oroszlan S., Shapiro B., Maizel J., Lowy D., Scolnick E. Nucleotide sequence of the p21 transforming protein of Harvey murine sarcoma virus. Science. 1982 Sep 3;217(4563):934–936. doi: 10.1126/science.6287572. [DOI] [PubMed] [Google Scholar]
  9. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  10. Eva A., Robbins K. C., Andersen P. R., Srinivasan A., Tronick S. R., Reddy E. P., Ellmore N. W., Galen A. T., Lautenberger J. A., Papas T. S. Cellular genes analogous to retroviral onc genes are transcribed in human tumour cells. Nature. 1982 Jan 14;295(5845):116–119. doi: 10.1038/295116a0. [DOI] [PubMed] [Google Scholar]
  11. Garrett J. S., Coughlin S. R., Niman H. L., Tremble P. M., Giels G. M., Williams L. T. Blockade of autocrine stimulation in simian sarcoma virus-transformed cells reverses down-regulation of platelet-derived growth factor receptors. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7466–7470. doi: 10.1073/pnas.81.23.7466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gentry L. E., Rohrschneider L. R., Casnellie J. E., Krebs E. G. Antibodies to a defined region of pp60src neutralize the tyrosine-specific kinase activity. J Biol Chem. 1983 Sep 25;258(18):11219–11228. [PubMed] [Google Scholar]
  13. Giallongo A., Appella E., Ricciardi R., Rovera G., Croce C. M. Identification of the c-myc oncogene product in normal and malignant B cells. Science. 1983 Oct 28;222(4622):430–432. doi: 10.1126/science.6604943. [DOI] [PubMed] [Google Scholar]
  14. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  15. Hampe A., Laprevotte I., Galibert F., Fedele L. A., Sherr C. J. Nucleotide sequences of feline retroviral oncogenes (v-fes) provide evidence for a family of tyrosine-specific protein kinase genes. Cell. 1982 Oct;30(3):775–785. doi: 10.1016/0092-8674(82)90282-3. [DOI] [PubMed] [Google Scholar]
  16. Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johnsson A., Heldin C. H., Wasteson A., Westermark B., Deuel T. F., Huang J. S., Seeburg P. H., Gray A., Ullrich A., Scrace G. The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor. EMBO J. 1984 May;3(5):921–928. doi: 10.1002/j.1460-2075.1984.tb01908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Josephs S. F., Guo C., Ratner L., Wong-Staal F. Human-proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus. Science. 1984 Feb 3;223(4635):487–491. doi: 10.1126/science.6318322. [DOI] [PubMed] [Google Scholar]
  19. Kelly K., Cochran B. H., Stiles C. D., Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. doi: 10.1016/0092-8674(83)90092-2. [DOI] [PubMed] [Google Scholar]
  20. Kruijer W., Cooper J. A., Hunter T., Verma I. M. Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and protein. Nature. 1984 Dec 20;312(5996):711–716. doi: 10.1038/312711a0. [DOI] [PubMed] [Google Scholar]
  21. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  22. Lerner R. A., Green N., Alexander H., Liu F. T., Sutcliffe J. G., Shinnick T. M. Chemically synthesized peptides predicted from the nucleotide sequence of the hepatitis B virus genome elicit antibodies reactive with the native envelope protein of Dane particles. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3403–3407. doi: 10.1073/pnas.78.6.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mohanachari V., Satyavelu Reddy K., Indira K. Ethanol-induced alterations in rat hepatic ammonia metabolism. Biochem Pharmacol. 1983 Sep 15;32(18):2825–2827. doi: 10.1016/0006-2952(83)90100-4. [DOI] [PubMed] [Google Scholar]
  24. Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
  25. Müller R., Slamon D. J., Adamson E. D., Tremblay J. M., Müller D., Cline M. J., Verma I. M. Transcription of c-onc genes c-rasKi and c-fms during mouse development. Mol Cell Biol. 1983 Jun;3(6):1062–1069. doi: 10.1128/mcb.3.6.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Müller R., Slamon D. J., Tremblay J. M., Cline M. J., Verma I. M. Differential expression of cellular oncogenes during pre- and postnatal development of the mouse. Nature. 1982 Oct 14;299(5884):640–644. doi: 10.1038/299640a0. [DOI] [PubMed] [Google Scholar]
  27. Niman H. L. Antisera to a synthetic peptide of the sis viral oncogene product recognize human platelet-derived growth factor. Nature. 1984 Jan 12;307(5947):180–183. doi: 10.1038/307180a0. [DOI] [PubMed] [Google Scholar]
  28. Niman H. L., Elder J. H. Molecular dissection of Rauscher virus gp70 by using monoclonal antibodies: localization of acquired sequences of related envelope gene recombinants. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4524–4528. doi: 10.1073/pnas.77.8.4524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Niman H. L., Houghten R. A., Bowen-Pope D. F. Detection of high molecular weight forms of platelet-derived growth factor by sequence-specific antisera. Science. 1984 Nov 9;226(4675):701–703. doi: 10.1126/science.6494905. [DOI] [PubMed] [Google Scholar]
  30. Niman H. L., Houghten R. A., Walker L. E., Reisfeld R. A., Wilson I. A., Hogle J. M., Lerner R. A. Generation of protein-reactive antibodies by short peptides is an event of high frequency: implications for the structural basis of immune recognition. Proc Natl Acad Sci U S A. 1983 Aug;80(16):4949–4953. doi: 10.1073/pnas.80.16.4949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Papkoff J., Verma I. M., Hunter T. Detection of a transforming gene product in cells transformed by Moloney murine sarcoma virus. Cell. 1982 Jun;29(2):417–426. doi: 10.1016/0092-8674(82)90158-1. [DOI] [PubMed] [Google Scholar]
  32. Ross R., Glomset J., Kariya B., Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1207–1210. doi: 10.1073/pnas.71.4.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
  34. Seifert R. A., Schwartz S. M., Bowen-Pope D. F. Developmentally regulated production of platelet-derived growth factor-like molecules. Nature. 1984 Oct 18;311(5987):669–671. doi: 10.1038/311669a0. [DOI] [PubMed] [Google Scholar]
  35. Sen S., Houghten R. A., Sherr C. J., Sen A. Antibodies of predetermined specificity detect two retroviral oncogene products and inhibit their kinase activities. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1246–1250. doi: 10.1073/pnas.80.5.1246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Shih T. Y., Papageorge A. G., Stokes P. E., Weeks M. O., Scolnick E. M. Guanine nucleotide-binding and autophosphorylating activities associated with the p21src protein of Harvey murine sarcoma virus. Nature. 1980 Oct 23;287(5784):686–691. doi: 10.1038/287686a0. [DOI] [PubMed] [Google Scholar]
  37. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  38. Tamura T., Bauer H., Birr C., Pipkorn R. Antibodies against synthetic peptides as a tool for functional analysis of the transforming protein pp60src. Cell. 1983 Sep;34(2):587–596. doi: 10.1016/0092-8674(83)90391-4. [DOI] [PubMed] [Google Scholar]
  39. Taparowsky E., Shimizu K., Goldfarb M., Wigler M. Structure and activation of the human N-ras gene. Cell. 1983 Sep;34(2):581–586. doi: 10.1016/0092-8674(83)90390-2. [DOI] [PubMed] [Google Scholar]
  40. Thor A., Horan Hand P., Wunderlich D., Caruso A., Muraro R., Schlom J. Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases. Nature. 1984 Oct 11;311(5986):562–565. doi: 10.1038/311562a0. [DOI] [PubMed] [Google Scholar]
  41. Toda T., Uno I., Ishikawa T., Powers S., Kataoka T., Broek D., Cameron S., Broach J., Matsumoto K., Wigler M. In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell. 1985 Jan;40(1):27–36. doi: 10.1016/0092-8674(85)90305-8. [DOI] [PubMed] [Google Scholar]
  42. Tsuchida N., Ryder T., Ohtsubo E. Nucleotide sequence of the oncogene encoding the p21 transforming protein of Kirsten murine sarcoma virus. Science. 1982 Sep 3;217(4563):937–939. doi: 10.1126/science.6287573. [DOI] [PubMed] [Google Scholar]
  43. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  44. Westin E. H., Wong-Staal F., Gelmann E. P., Dalla-Favera R., Papas T. S., Lautenberger J. A., Eva A., Reddy E. P., Tronick S. R., Aaronson S. A. Expression of cellular homologues of retroviral onc genes in human hematopoietic cells. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2490–2494. doi: 10.1073/pnas.79.8.2490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wong T. W., Goldberg A. R. Synthetic peptide fragment of src gene product inhibits the src protein kinase and crossreacts immunologically with avian onc kinases and cellular phosphoproteins. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7412–7416. doi: 10.1073/pnas.78.12.7412. [DOI] [PMC free article] [PubMed] [Google Scholar]

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