Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1989 Feb 1;108(2):267–276. doi: 10.1083/jcb.108.2.267

Carcinoembryonic antigens: alternative splicing accounts for the multiple mRNAs that code for novel members of the carcinoembryonic antigen family

PMCID: PMC2115422  PMID: 2537311

Abstract

The recent cloning of complete cDNAs encoding carcinoembryonic antigen (CEA) and non-specific cross-reacting antigen has revealed the existence of a new gene family belonging to the immunoglobulin gene superfamily. We have reported the isolation of a partial CEA cDNA and of L-cell transfectant cell lines that express human antigens cross- reactive with commercial antibodies directed to native CEA (Kamarck, M., J. Elting, J. Hart, S. Goebel, P. M. M. Rae, J. Nedwin, and T. Barnett. 1987. Proc. Natl. Acad. Sci. USA. 84:5350-5354). In this study, we describe the identification and cloning of 3.9-, 3.7-, 2.2-, and 1.8-kb cDNAs and a 23-kb genomic transcription unit, which code for new members of the CEA gene family. DNA sequence analysis of these cloned DNAs establishes the existence of a set of four alternatively spliced mRNAs which are expressed in several tumor cell lines, in human fetal liver, and in L-cell transfectants. Deduced amino acid sequences of the encoded isoantigens show extensive similarity to CEA and nonspecific cross-reacting antigens, but in addition demonstrate transmembrane and cytoplasmic domains. We designate members of this antigen family transmembrane CEAs. The transmembrane CEA isoantigens share general structural characteristics with members of the immunoglobulin gene superfamily and can be specifically compared to the cell adhesion molecules, N-CAM (neural cell adhesion molecule) and MAG (myelin-associated glycoprotein).

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Arquint M., Roder J., Chia L. S., Down J., Wilkinson D., Bayley H., Braun P., Dunn R. Molecular cloning and primary structure of myelin-associated glycoprotein. Proc Natl Acad Sci U S A. 1987 Jan;84(2):600–604. doi: 10.1073/pnas.84.2.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnett T., Goebel S. J., Nothdurft M. A., Elting J. J. Carcinoembryonic antigen family: characterization of cDNAs coding for NCA and CEA and suggestion of nonrandom sequence variation in their conserved loop-domains. Genomics. 1988 Jul;3(1):59–66. doi: 10.1016/0888-7543(88)90160-7. [DOI] [PubMed] [Google Scholar]
  4. Beauchemin N., Benchimol S., Cournoyer D., Fuks A., Stanners C. P. Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen. Mol Cell Biol. 1987 Sep;7(9):3221–3230. doi: 10.1128/mcb.7.9.3221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  6. Bonthron D. T., Morton C. C., Orkin S. H., Collins T. Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1492–1496. doi: 10.1073/pnas.85.5.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Caras I. W., Davitz M. A., Rhee L., Weddell G., Martin D. W., Jr, Nussenzweig V. Cloning of decay-accelerating factor suggests novel use of splicing to generate two proteins. Nature. 1987 Feb 5;325(6104):545–549. doi: 10.1038/325545a0. [DOI] [PubMed] [Google Scholar]
  8. Cunningham B. A., Hemperly J. J., Murray B. A., Prediger E. A., Brackenbury R., Edelman G. M. Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science. 1987 May 15;236(4803):799–806. doi: 10.1126/science.3576199. [DOI] [PubMed] [Google Scholar]
  9. Darcy D. A., Turberville C., James R. Immunological study of carcinoembryonic antigen (CEA) and a related glycoprotein. Br J Cancer. 1973 Aug;28(2):147–160. doi: 10.1038/bjc.1973.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DiLella A. G., Woo S. L. Cloning large segments of genomic DNA using cosmid vectors. Methods Enzymol. 1987;152:199–212. doi: 10.1016/0076-6879(87)52021-3. [DOI] [PubMed] [Google Scholar]
  11. Dickson G., Gower H. J., Barton C. H., Prentice H. M., Elsom V. L., Moore S. E., Cox R. D., Quinn C., Putt W., Walsh F. S. Human muscle neural cell adhesion molecule (N-CAM): identification of a muscle-specific sequence in the extracellular domain. Cell. 1987 Sep 25;50(7):1119–1130. doi: 10.1016/0092-8674(87)90178-4. [DOI] [PubMed] [Google Scholar]
  12. Engvall E., Shively J. E., Wrann M. Isolation and characterization of the normal crossreacting antigen: homology of its NH2-terminal amino acid sequence with that of carcinoembryonic antigen. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1670–1674. doi: 10.1073/pnas.75.4.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  14. Gold P., Freedman S. O. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965 Sep 1;122(3):467–481. doi: 10.1084/jem.122.3.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  16. Hampe A., Gobet M., Sherr C. J., Galibert F. Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. Proc Natl Acad Sci U S A. 1984 Jan;81(1):85–89. doi: 10.1073/pnas.81.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  18. Hunkapiller T., Hood L. The growing immunoglobulin gene superfamily. Nature. 1986 Sep 4;323(6083):15–16. doi: 10.1038/323015a0. [DOI] [PubMed] [Google Scholar]
  19. Kamarck M. E., Elting J. J., Hart J. T., Goebel S. J., Rae P. M., Nothdurft M. A., Nedwin J. J., Barnett T. R. Carcinoembryonic antigen family: expression in a mouse L-cell transfectant and characterization of a partial cDNA in bacteriophage lambda gt11. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5350–5354. doi: 10.1073/pnas.84.15.5350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  22. Maddon P. J., Littman D. R., Godfrey M., Maddon D. E., Chess L., Axel R. The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell. 1985 Aug;42(1):93–104. doi: 10.1016/s0092-8674(85)80105-7. [DOI] [PubMed] [Google Scholar]
  23. Mullins J. I., Brody D. S., Binari R. C., Jr, Cotter S. M. Viral transduction of c-myc gene in naturally occurring feline leukaemias. 1984 Apr 26-May 2Nature. 308(5962):856–858. doi: 10.1038/308856a0. [DOI] [PubMed] [Google Scholar]
  24. Neumaier M., Fenger U., Wagener C. Monoclonal antibodies for carcinoembryonic antigen (CEA) as a model system: identification of two novel CEA-related antigens in meconium and colorectal carcinoma tissue by Western blots and differential immunoaffinity chromatography. J Immunol. 1985 Nov;135(5):3604–3609. [PubMed] [Google Scholar]
  25. Neumaier M., Zimmermann W., Shively L., Hinoda Y., Riggs A. D., Shively J. E. Characterization of a cDNA clone for the nonspecific cross-reacting antigen (NCA) and a comparison of NCA and carcinoembryonic antigen. J Biol Chem. 1988 Mar 5;263(7):3202–3207. [PubMed] [Google Scholar]
  26. Oikawa S., Nakazato H., Kosaki G. Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence. Biochem Biophys Res Commun. 1987 Jan 30;142(2):511–518. doi: 10.1016/0006-291x(87)90304-4. [DOI] [PubMed] [Google Scholar]
  27. Paxton R. J., Mooser G., Pande H., Lee T. D., Shively J. E. Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family. Proc Natl Acad Sci U S A. 1987 Feb;84(4):920–924. doi: 10.1073/pnas.84.4.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Peterson A., Seed B. Monoclonal antibody and ligand binding sites of the T cell erythrocyte receptor (CD2). 1987 Oct 29-Nov 4Nature. 329(6142):842–846. doi: 10.1038/329842a0. [DOI] [PubMed] [Google Scholar]
  29. Salzer J. L., Holmes W. P., Colman D. R. The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. J Cell Biol. 1987 Apr;104(4):957–965. doi: 10.1083/jcb.104.4.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shively J. E., Beatty J. D. CEA-related antigens: molecular biology and clinical significance. Crit Rev Oncol Hematol. 1985;2(4):355–399. doi: 10.1016/s1040-8428(85)80008-1. [DOI] [PubMed] [Google Scholar]
  32. Simmons D., Makgoba M. W., Seed B. ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature. 1988 Feb 18;331(6157):624–627. doi: 10.1038/331624a0. [DOI] [PubMed] [Google Scholar]
  33. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  34. Takami N., Misumi Y., Kuroki M., Matsuoka Y., Ikehara Y. Evidence for carboxyl-terminal processing and glycolipid-anchoring of human carcinoembryonic antigen. J Biol Chem. 1988 Sep 5;263(25):12716–12720. [PubMed] [Google Scholar]
  35. Tarentino A. L., Gómez C. M., Plummer T. H., Jr Deglycosylation of asparagine-linked glycans by peptide:N-glycosidase F. Biochemistry. 1985 Aug 13;24(17):4665–4671. doi: 10.1021/bi00338a028. [DOI] [PubMed] [Google Scholar]
  36. Tawaragi Y., Oikawa S., Matsuoka Y., Kosaki G., Nakazato H. Primary structure of nonspecific crossreacting antigen (NCA), a member of carcinoembryonic antigen (CEA) gene family, deduced from cDNA sequence. Biochem Biophys Res Commun. 1988 Jan 15;150(1):89–96. doi: 10.1016/0006-291x(88)90490-1. [DOI] [PubMed] [Google Scholar]
  37. Thompson J. A., Pande H., Paxton R. J., Shively L., Padma A., Simmer R. L., Todd C. W., Riggs A. D., Shively J. E. Molecular cloning of a gene belonging to the carcinoembryonic antigen gene family and discussion of a domain model. Proc Natl Acad Sci U S A. 1987 May;84(9):2965–2969. doi: 10.1073/pnas.84.9.2965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tong B. D., Auer D. E., Jaye M., Kaplow J. M., Ricca G., McConathy E., Drohan W., Deuel T. F. cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains. Nature. 1987 Aug 13;328(6131):619–621. doi: 10.1038/328619a0. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Wickens M., Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. doi: 10.1126/science.6208611. [DOI] [PubMed] [Google Scholar]
  41. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  42. Williams A. F., Gagnon J. Neuronal cell Thy-1 glycoprotein: homology with immunoglobulin. Science. 1982 May 14;216(4547):696–703. doi: 10.1126/science.6177036. [DOI] [PubMed] [Google Scholar]
  43. Yarden Y., Escobedo J. A., Kuang W. J., Yang-Feng T. L., Daniel T. O., Tremble P. M., Chen E. Y., Ando M. E., Harkins R. N., Francke U. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature. 1986 Sep 18;323(6085):226–232. doi: 10.1038/323226a0. [DOI] [PubMed] [Google Scholar]
  44. von Kleist S., Chavanel G., Burtin P. Identification of an antigen from normal human tissue that crossreacts with the carcinoembryonic antigen. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2492–2494. doi: 10.1073/pnas.69.9.2492. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES