erbB-2 antisense oligonucleotides inhibit the proliferation of breast carcinoma cells with erbB-2 oncogene amplification (original) (raw)

Abstract

Amplification and overexpression of the erbB-2 oncogene is an unfavourable prognostic marker in human breast cancer and occurs in approximately 25% of breast carcinomas. We used erbB-2 antisense oligonucleotides to inhibit the proliferation of human breast cancer cell lines. erbB-2 antisense oligonucleotides (20 microM) inhibited the growth and DNA synthesis of breast cancer cell lines with an amplified erbB-2 gene by up to 60%. Control complementary sense oligonucleotides did not inhibit cellular proliferation at the same concentration but showed inhibitory effects at higher concentrations. There was no specific effect of erbB-2 antisense oligonucleotides on breast cancer cell lines that had no amplification of erbB-2. erbB-2 antisense oligonucleotides reduced erbB-2 protein levels, measured by immunohistochemistry, in a dose-dependent manner. erbB-2 sense oligonucleotides did not decrease the levels of erbB-2 protein. These data indicate that erbB-2 antisense oligonucleotides induce a specific inhibition of erbB-2 protein expression and that erbB-2 gene overexpression is important for the proliferation of the breast cancer cells that have been selected for erbB-2 amplification.

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  1. Bacus S. S., Bacus J. W., Slamon D. J., Press M. F. HER-2/neu oncogene expression and DNA ploidy analysis in breast cancer. Arch Pathol Lab Med. 1990 Feb;114(2):164–169. [PubMed] [Google Scholar]
  2. Bacus S. S., Huberman E., Chin D., Kiguchi K., Simpson S., Lippman M., Lupu R. A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human breast cancer cells. Cell Growth Differ. 1992 Jul;3(7):401–411. [PubMed] [Google Scholar]
  3. Bouchard L., Lamarre L., Tremblay P. J., Jolicoeur P. Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Cell. 1989 Jun 16;57(6):931–936. doi: 10.1016/0092-8674(89)90331-0. [DOI] [PubMed] [Google Scholar]
  4. Carter G., Lemoine N. R. Antisense technology for cancer therapy: does it make sense? Br J Cancer. 1993 May;67(5):869–876. doi: 10.1038/bjc.1993.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coussens L., Yang-Feng T. L., Liao Y. C., Chen E., Gray A., McGrath J., Seeburg P. H., Libermann T. A., Schlessinger J., Francke U. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132–1139. doi: 10.1126/science.2999974. [DOI] [PubMed] [Google Scholar]
  6. Di Fiore P. P., Pierce J. H., Kraus M. H., Segatto O., King C. R., Aaronson S. A. erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. Science. 1987 Jul 10;237(4811):178–182. doi: 10.1126/science.2885917. [DOI] [PubMed] [Google Scholar]
  7. Drebin J. A., Link V. C., Greene M. I. Monoclonal antibodies specific for the neu oncogene product directly mediate anti-tumor effects in vivo. Oncogene. 1988 Apr;2(4):387–394. [PubMed] [Google Scholar]
  8. Drebin J. A., Link V. C., Stern D. F., Weinberg R. A., Greene M. I. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell. 1985 Jul;41(3):697–706. doi: 10.1016/s0092-8674(85)80050-7. [DOI] [PubMed] [Google Scholar]
  9. Drebin J. A., Link V. C., Weinberg R. A., Greene M. I. Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9129–9133. doi: 10.1073/pnas.83.23.9129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holt J. T., Redner R. L., Nienhuis A. W. An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentiation. Mol Cell Biol. 1988 Feb;8(2):963–973. doi: 10.1128/mcb.8.2.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Horiguchi J., Sherman M. L., Sampson-Johannes A., Weber B. L., Kufe D. W. CSF-1 and C-FMS gene expression in human carcinoma cell lines. Biochem Biophys Res Commun. 1988 Nov 30;157(1):395–401. doi: 10.1016/s0006-291x(88)80060-3. [DOI] [PubMed] [Google Scholar]
  12. Hudziak R. M., Lewis G. D., Winget M., Fendly B. M., Shepard H. M., Ullrich A. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol Cell Biol. 1989 Mar;9(3):1165–1172. doi: 10.1128/mcb.9.3.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hudziak R. M., Schlessinger J., Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7159–7163. doi: 10.1073/pnas.84.20.7159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Iglehart J. D., Kraus M. H., Langton B. C., Huper G., Kerns B. J., Marks J. R. Increased erbB-2 gene copies and expression in multiple stages of breast cancer. Cancer Res. 1990 Oct 15;50(20):6701–6707. [PubMed] [Google Scholar]
  15. Kraus M. H., Issing W., Miki T., Popescu N. C., Aaronson S. A. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9193–9197. doi: 10.1073/pnas.86.23.9193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kraus M. H., Popescu N. C., Amsbaugh S. C., King C. R. Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J. 1987 Mar;6(3):605–610. doi: 10.1002/j.1460-2075.1987.tb04797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kumar R., Shepard H. M., Mendelsohn J. Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol Cell Biol. 1991 Feb;11(2):979–986. doi: 10.1128/mcb.11.2.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lupu R., Colomer R., Zugmaier G., Sarup J., Shepard M., Slamon D., Lippman M. E. Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2. Science. 1990 Sep 28;249(4976):1552–1555. doi: 10.1126/science.2218496. [DOI] [PubMed] [Google Scholar]
  19. Maguire H. C., Jr, Greene M. I. The neu (c-erbB-2) oncogene. Semin Oncol. 1989 Apr;16(2):148–155. [PubMed] [Google Scholar]
  20. McManaway M. E., Neckers L. M., Loke S. L., al-Nasser A. A., Redner R. L., Shiramizu B. T., Goldschmidts W. L., Huber B. E., Bhatia K., Magrath I. T. Tumour-specific inhibition of lymphoma growth by an antisense oligodeoxynucleotide. Lancet. 1990 Apr 7;335(8693):808–811. doi: 10.1016/0140-6736(90)90934-w. [DOI] [PubMed] [Google Scholar]
  21. Melani C., Rivoltini L., Parmiani G., Calabretta B., Colombo M. P. Inhibition of proliferation by c-myb antisense oligodeoxynucleotides in colon adenocarcinoma cell lines that express c-myb. Cancer Res. 1991 Jun 1;51(11):2897–2901. [PubMed] [Google Scholar]
  22. Morrison R. S. Suppression of basic fibroblast growth factor expression by antisense oligodeoxynucleotides inhibits the growth of transformed human astrocytes. J Biol Chem. 1991 Jan 15;266(2):728–734. [PubMed] [Google Scholar]
  23. Muller W. J., Sinn E., Pattengale P. K., Wallace R., Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell. 1988 Jul 1;54(1):105–115. doi: 10.1016/0092-8674(88)90184-5. [DOI] [PubMed] [Google Scholar]
  24. Paik S., Hazan R., Fisher E. R., Sass R. E., Fisher B., Redmond C., Schlessinger J., Lippman M. E., King C. R. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol. 1990 Jan;8(1):103–112. doi: 10.1200/JCO.1990.8.1.103. [DOI] [PubMed] [Google Scholar]
  25. Plowman G. D., Whitney G. S., Neubauer M. G., Green J. M., McDonald V. L., Todaro G. J., Shoyab M. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci U S A. 1990 Jul;87(13):4905–4909. doi: 10.1073/pnas.87.13.4905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Press M. F., Cordon-Cardo C., Slamon D. J. Expression of the HER-2/neu proto-oncogene in normal human adult and fetal tissues. Oncogene. 1990 Jul;5(7):953–962. [PubMed] [Google Scholar]
  27. Reed J. C., Stein C., Subasinghe C., Haldar S., Croce C. M., Yum S., Cohen J. Antisense-mediated inhibition of BCL2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides. Cancer Res. 1990 Oct 15;50(20):6565–6570. [PubMed] [Google Scholar]
  28. Rosolen A., Whitesell L., Ikegaki N., Kennett R. H., Neckers L. M. Antisense inhibition of single copy N-myc expression results in decreased cell growth without reduction of c-myc protein in a neuroepithelioma cell line. Cancer Res. 1990 Oct 1;50(19):6316–6322. [PubMed] [Google Scholar]
  29. Ryte A., Morelli S., Mazzei M., Alama A., Franco P., Canti G. F., Nicolin A. Oligonucleotide degradation contributes to resistance to antisense compounds. Anticancer Drugs. 1993 Apr;4(2):197–200. doi: 10.1097/00001813-199304000-00011. [DOI] [PubMed] [Google Scholar]
  30. Saison-Behmoaras T., Tocqué B., Rey I., Chassignol M., Thuong N. T., Hélène C. Short modified antisense oligonucleotides directed against Ha-ras point mutation induce selective cleavage of the mRNA and inhibit T24 cells proliferation. EMBO J. 1991 May;10(5):1111–1118. doi: 10.1002/j.1460-2075.1991.tb08051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sarup J. C., Johnson R. M., King K. L., Fendly B. M., Lipari M. T., Napier M. A., Ullrich A., Shepard H. M. Characterization of an anti-p185HER2 monoclonal antibody that stimulates receptor function and inhibits tumor cell growth. Growth Regul. 1991 Jun;1(2):72–82. [PubMed] [Google Scholar]
  32. Schechter A. L., Hung M. C., Vaidyanathan L., Weinberg R. A., Yang-Feng T. L., Francke U., Ullrich A., Coussens L. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985 Sep 6;229(4717):976–978. doi: 10.1126/science.2992090. [DOI] [PubMed] [Google Scholar]
  33. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  34. Szczylik C., Skorski T., Nicolaides N. C., Manzella L., Malaguarnera L., Venturelli D., Gewirtz A. M., Calabretta B. Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. Science. 1991 Aug 2;253(5019):562–565. doi: 10.1126/science.1857987. [DOI] [PubMed] [Google Scholar]
  35. Tagliabue E., Centis F., Campiglio M., Mastroianni A., Martignone S., Pellegrini R., Casalini P., Lanzi C., Ménard S., Colnaghi M. I. Selection of monoclonal antibodies which induce internalization and phosphorylation of p185HER2 and growth inhibition of cells with HER2/NEU gene amplification. Int J Cancer. 1991 Apr 1;47(6):933–937. doi: 10.1002/ijc.2910470625. [DOI] [PubMed] [Google Scholar]
  36. Tandon A. K., Clark G. M., Chamness G. C., Ullrich A., McGuire W. L. HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol. 1989 Aug;7(8):1120–1128. doi: 10.1200/JCO.1989.7.8.1120. [DOI] [PubMed] [Google Scholar]
  37. Tarakhovsky A. M., Resnikov M., Zaichuk T., Tugusheva M. V., Butenko Z. A., Prassolov V. S. Polymorphic changes of cell phenotype caused by elevated expression of an exogenous NEU proto-oncogene. Oncogene. 1990 Mar;5(3):405–410. [PubMed] [Google Scholar]
  38. Tidd D. M. A potential role for antisense oligonucleotide analogues in the development of oncogene targeted cancer chemotherapy. Anticancer Res. 1990 Sep-Oct;10(5A):1169–1182. [PubMed] [Google Scholar]
  39. Wickstrom E. L., Bacon T. A., Gonzalez A., Freeman D. L., Lyman G. H., Wickstrom E. Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1028–1032. doi: 10.1073/pnas.85.4.1028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wright C., Angus B., Nicholson S., Sainsbury J. R., Cairns J., Gullick W. J., Kelly P., Harris A. L., Horne C. H. Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. Cancer Res. 1989 Apr 15;49(8):2087–2090. [PubMed] [Google Scholar]
  41. Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. doi: 10.1038/319230a0. [DOI] [PubMed] [Google Scholar]
  42. van Leeuwen F., van de Vijver M. J., Lomans J., van Deemter L., Jenster G., Akiyama T., Yamamoto T., Nusse R. Mutation of the human neu protein facilitates down-modulation by monoclonal antibodies. Oncogene. 1990 Apr;5(4):497–503. [PubMed] [Google Scholar]