Abstract
An enzyme‐linked immunosorbent assay (ELISA) was developed to measure soluble erbB‐2 protein in culture supernatants of various human cell lines and sera of patients suffering from recurrent breast carcinoma. Soluble erbB‐2 protein was demonstrated in culture supernatants of cell lines that expressed high levels of erbB‐2 protein as shown by western blot analysis of cell lysates. Increased levels of the protein, 40‐ to 190‐fold higher than in healthy controls, were demonstrated in sera of 3 out of 12 patients with breast carcinomas. On immunohistological study of tumor tissues from 9 patients, high immune reaction with the anti‐erbB‐2 protein antibody was observed in 2 cases. These were two of the three patients who had elevated levels of erbB‐2 protein in serum (a sample was not available from the third patient). These results raise the possibility that soluble erbB‐2 protein level in serum can be used as an indicator for spread of carcinomas that overexpress erbB‐2 protein.
Keywords: Receptor, Oncogene, Carcinoma, Membrane protein, Breast
Full Text
The Full Text of this article is available as a PDF (469.3 KB).
REFERENCES
- 1. ) Semba , K. , Kamata , N. , Toyoshima , K. and Yamamoto , T.A v‐erbB‐related protooncogene, erbB‐2, is distinct from the c‐erbB‐1/epidermal growth factor‐receptor gene and is amplified in human salivary gland adenocarcinoma . Proc. Natl. Acad. Sci. USA , 82 , 6497 – 6501 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. ) Schechter , A. L. , Hung , M. C. , Vaidyanathan , L. , Weinberg , R. A. , Yang‐Feng , T. L. , Franke , U. , Ullrich , A. and Coussens , L.The neu gene: an erbB‐homologous gene distinct from and unlinked to the gene encoding the EGF receptor . Science , 229 , 976 – 979 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Coussens , L. , Yang‐Feng , T. L. , Liao , Y‐C. , Chen , E. , Gray , A. , McGrath , J. , Seenburg , P. H. , Levinson , A. and Ullrich , A.Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene . Science , 230 , 1132 – 1139 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Akiyama , T. , Sudo , C. , Ogawara , H. , Toyoshima , K. and Yamamoto , T.The product of human c‐erbB‐2 gene: a 185 kilodalton glycoprotein with tyrosine‐kinase activity . Science , 232 , 1644 – 1646 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Bargmann , C. I. , Hung , M. C. and Weinberg , R. A.The neu oncogene encodes an epidermal growth factor receptor‐related protein . Nature , 319 , 226 – 230 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Yokota , J. , Yamamoto , T. , Toyoshima , K. , Terada , M. , Sugimura , T. , Battifora , H. and Cline , M. J.Amplification of c‐erbB‐2 oncogene in human adenocarcinomas in vivo . Lancet , i , 765 – 767 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Fukushige , S. , Matsubara , K. , Yoshida , M. , Sakai , M. , Suzuki , T. , Semba , K. , Toyoshima , K. and Yamamoto , T.Localization of a novel v‐erbB related gene, c‐erbB‐2, on human chromosome 17 and its amplification in a gastric cancer cell line . Mol. Cell Biol. , 6 , 955 – 958 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Mori , S. , Akiyama , T. , Morishita , Y. , Shimizu , S. , Sakai , K. , Sudoh , K. , Toyoshima , K. and Yamamoto , T.Light and electron‐microscopical demonstration of c‐erbB‐2 gene product‐like immunoreactivity in human malignant tumors . Virchows Arch. B , 54 , 8 – 15 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Slamon , D. J. , Clark , G. M. , Wong , S. G. , Levin , W. J. , Ullrich , A. and McGuire , W. L.Human breast cancer: correlation of relapse and survival with amplification of the HER‐2/neu oncogene . Science , 235 , 177 – 182 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Gusterson , B. A. , Machin , L. G. , Gullick , W. G. , Gibbs , N. M. , Powles , T. J. , Elliott , C. , Ashley , S. , Monaghan , P. and Harrison , S.C‐erbB‐2 expression in benign and malignant breast disease . Br. J. Cancer , 58 , 453 – 457 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Barnes , D. M. , Lammie , G. A. , Mills , R. R. , Gullick , W. L. , Allen , D. S. and Altman , D. G.An immunohistochemical evaluation of c‐erbB‐2 expression in human breast carcinoma . Br. J. Cancer , 58 , 448 – 452 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. ) Gavin , J. G. , IIIBuell , D. N. and Roth , J.Water‐soluble insulin receptor from human lymphocytes . Science , 178 , 178 – 179 ( 1972. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Weber , W. , Gill , G. N. and Spiess , J.Production of an epidermal growth factor receptor‐related protein . Science , 224 , 294 – 297 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Rubin , L. A. , Kurman , C. C. , Fritz , M. E. , Biddison , W. E. , Boutin , B. , Yarchoan , R. and Nelson , D. L.Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro . J. Immunol. , 135 , 3172 – 3177 ( 1985. ). [PubMed] [Google Scholar]
- 15. ) Kraus , M. H. , Popescu , N. C. , Amsbaugh , S. C. and King , C. R.Overexpression of the EGF receptor‐related protooncogene erbB‐2 in human mammary tumor cell lines by different molecular mechanisms . EMBO J. , 6 , 606 – 610 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. ) Masuko , T. , Sugahara , K. , Kozono , M. , Otsuki , S. , Akiyama , T. , Yamamoto , T. , Toyoshima , K. and Hashimoto , Y.A murine monoclonal antibody that recognizes an extracellular domain of the human c‐erbB‐2 protooncogene product . Jpn. J. Cancer Res. , 80 , 10 – 14 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. ) Van de Vijver , M. J. , Peterse , J. L. , Mooi , W. J. , Wisman , P. , Lomans , J. , Dalesio , O. and Nusse , R.neu‐protein overexpression in breast cancer. Association with comedo‐type ductal carcinoma in situ and limited prognostic value in stage II breast cancer . N. Engl. J. Med. , 319 , 1239 – 1245 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Mori , S. , Akiyama , T. , Yamada , Y. , Morishita , Y. , Sugawara , I. , Toyoshima , K. and Yamamoto , T.C‐erbB‐2 gene product, a membrane protein commonly expressed on human fetal epithelial cells . Lab. Invest. , 54 , 8 – 15 ( 1989. ). [PubMed] [Google Scholar]
- 19. ) Hsu , S. M. , Rayne , L. and Fanger , H.Use of avidinbiotin‐peroxidase complex (ABC) in immunoperoxidase techniques . J. Histochem. Cytochem. , 29 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]