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Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines

  • Original Papers
  • Experimental Oncology
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Summary

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell lines, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype, v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we founderbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene likeerbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.

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Abbreviations

kb:

kilobase(s)

SSC:

saline sodium citrate (1×SSC is 0.15 M sodium chloride: 0.015 M sodium citrate)

oligo(dT):

oligodeoxythymidylate

SDS:

sodium dodecylsulfate

SCLC:

small cell lung cancer

NSCLC:

non-small-cell lung cancer

EGF:

epidermal growth factor

PDGF:

platelet-derived growth factor

References

  • Alitalo K, Schwab M, Lin CC, Varmus HE, Bishop JM (1983) Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci USA 80:1707–1711

    Google Scholar 

  • Alt FW, DePinho R, Zimmermann K, Legouy E, Hatton K, Ferrier P, Tesfaye A, Yancopoulos G, Nisen P (1986) The humanmyc gene family. Cold Spring Harbor Symp Quant Biol 51:931–941

    Google Scholar 

  • Armelin HA, Armelin MCS, Kelly K, Stewart T, Leder P, Cochran BH, Stiles CD (1984) Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature 310:655–660

    Google Scholar 

  • Aviv H, Leder P (1972) Purification of biologically active globin messenger RNA by chromatography on oligo thymidylic acid-cellulose. Proc Natl Acad Sci USA 69:1408–1412

    Google Scholar 

  • Bepler G, Koehler A, Kiefer P, Havemann K, Beisenherz K, Jaques G, Gropp C (1988) Characterization of the state of differentiation of six newly established NSCLC cell lines. Differentiation 37:158–171

    Google Scholar 

  • Bergh J, Nilsson K, Zech L, Giovanella B (1981) Establishment and characterization of a continuous lung squamous cell carcinoma cell line (U-1752). Anticancer Res I: 317–322

    Google Scholar 

  • Bergh J, Ekman R, Giovanelli B, Nilsson K (1985) Establishment and characterization of cell lines from human small cell and large cell carcinoma of the lung. Acta Pathol Microbiol Immunol Scand AJ 93:133–147

    Google Scholar 

  • Betsholtz C, Bergh J, Bywater M, Pettersson M, Johnsson A, Heldin CH, Ohlsson R, Knott TJ, Scott J, Bell GI, Westermark B (1989) Expression of multiple growth factors in a human lung cancer cell line. Int J Cancer (in press)

  • Bishop JM (1983) Cellular oncogens and retroviruses. Annu Rev Biochem 52:301–354

    Google Scholar 

  • Bravo R, Burckhard J, Curran T, Müller R (1985) Stimulation and inhibition of growth by EGF in different A431 cell clones is accompanied by the rapid induction of c-fas and c-myc proto-oncogenes. EMBO J 4:1193–1197

    Google Scholar 

  • Capon DJ, Chen Y, Devinson AD, Seeburg PH, Goeddel DV (1983a) Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature 302:33–37

    Google Scholar 

  • Capon DJ, Seeburg PH, McGrath JP, Hayflick JS, Edman U, Levinson AD, Goeddel DV (1983b) Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations. Nature 304:507–513

    Google Scholar 

  • Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD (1985) Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45:2913–2923

    Google Scholar 

  • Chirgwin M, Przybyla AE, MacDonald RJ, Rutter WJ (1979) Preparation of biologically active revonucleic acid from sources rich in ribonuclease. Biochemistry 18:5294–5299

    Google Scholar 

  • Collins SJ, Groudine MT (1983) Rearrangement and amplification of c-ab1 sequences in the human chronic myelogenous leukemia cell line K-562. Proc Natl Acad Sci USA 80:4813–4817

    Google Scholar 

  • Coussens PM, Cooper JA, Hunter T, Shalloway D (1985) Restriction of the in vitro and in vivo tyrosine protein kinase activities of pr60c-src relative to pp60r-src. Mol Cell Biol 5:2753–2763

    Google Scholar 

  • Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC (1982a) Human c-myc oncogene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci (USA) 79:7824–7827

    Google Scholar 

  • Dalla-Favera R, Wong-Stall F, Gallo RC (1982b) Oncogene amplification in promyelocytic leukemia cell line HL60 and primary leukemic cells of the same patient. Nature 299:61–63

    Google Scholar 

  • DeLorbe WJ, Luciw PA, Goodman HM, Varmus HE, Bishop JM (1980) Molecular cloning and characterization of avian sarcoma virus circular molecules. J Virol 36:50–61

    Google Scholar 

  • Derynck R, Goeddel DV, Ulrich A, Gutterman JU, Williams RD, Bringman TS, Berger WH (1987) Synthesis of messenger RNAs for transforming growth factors a and b and the epidermal growth factor receptor by human tumors. Cancer Res 47:707–712

    Google Scholar 

  • Donner L, Fedele LA, Garon CF, Anderson SJ, Sherr CJ (1982) McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms). J Virol 41:489–500

    Google Scholar 

  • Duesberg PH (1985) Activated proto-oncogenes: sufficient or necessary for cancer? Science 228:669–677

    Google Scholar 

  • Gazdar AF, Carney DN, Nau MM, Minna JD (1985) Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological and growth properties. Cancer Res 45:2924–2930

    Google Scholar 

  • Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, Parks WP (1973) In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst 51:1417–1423

    Google Scholar 

  • Gonda TJ, Bishop JM (1983) Structure and transcription of the cellular homolog (c-myb) of the avian myeloblastosis virus transforming gene (v-myb). J Virol 46:212–220

    Google Scholar 

  • Goustin AS, Leor EB, Snipley GD, Moses HL (1986) Growth factors and cancer. Cancer Res 46:1015–1029

    Google Scholar 

  • Greenberg ME, Ziff EB (1984) Stimulation of 3T3 cells induces transcription of thec-fos proto-oncogene. Nature 311:433–438

    Google Scholar 

  • Griffin CA, Baylin SB (1985) Expression of the c-myb oncogene in human small cell lung cancer. Resent Results Cancer Res 99:237–245

    Google Scholar 

  • Groffen J, Stephenson JR, Heisterkamp N, deKlein A, Bartram CR, Grosveld G (1984) Philadelphia chromosomal breakpoints are clusterd within a limited region,bcr, on chromosome 22. Cell 36:93–99

    Google Scholar 

  • Haeder M, Rotsch M, Bepler G, Henning C, Havemann K, Heimann B, Moelling K (1988) Differences in EGF-receptor expression distinguish human non-small cell from small cell lung cancer. J Cancer Res 48:1132–1136

    Google Scholar 

  • Havemann K, Kiefer P, Haeder M, Hartogh G, Heimann B, Moelling K, Bepler G (1988) Oncogene expression in the spectrum of pulmonary carcinoma. International conference on hormones, growth factors and oncogenes in pulmonary carcinoma, Hanover, New Hampshire, USA, 30.8.–2.9.1988, Lung cancer

  • Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, deKlein A, Bartram CR, Grosveld G (1983) Localization of the c-ab1 oncogene adjacent to a translation break point in chronic myelocytic leukemia. Nature 306:239–242

    Google Scholar 

  • Hunter T, Cooper JA (1985) Protein-tyrosine kinases. Annu Rev Biochem 54:897–930

    Google Scholar 

  • Iba H, Takeya T, Cross F, Hanafusa T, Hanafusa H (1984) Rous sarcoma virus variants that carry the cellularsrc gene instead of the viralsrc gene cannot transform chicken embryo fibroblasts. Proc Natl Acad Sci USA 81:4424–4428

    Google Scholar 

  • Iba H, Gross FR, Garber EA, Hanafusa H (1985) Low level of cellular protein phosphorylation by nontransforming overproduced p60c-src. Mol Cell Biol 5:1058–1066

    Google Scholar 

  • Kelly K, Cochran BH, Stiles CD, Leder P (1983) Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet derived growth factor. Cell 35:603–610

    Google Scholar 

  • Kiefer P, Bepler G, Kubasch M, Havemann K (1987) Amplification and expression of proto-oncogenes in human small cell lung cancer cell lines. Cancer Res 47:6236–6242

    Google Scholar 

  • Klein G (1983) Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell 32:311–315

    Google Scholar 

  • Kolata G (1987) Oncogenes give breast cancer prognosis. Science 235:160–161

    Google Scholar 

  • Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD (1983) Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature 305:194–196

    Google Scholar 

  • Luttrell DK, Luttrell LM, Parsons SJ (1988) Augmented mitogenic responsivenes to epidermal growth factor in murine fibroblasts that overexpress pp60c-src molecular and cellular biology. Mol Cell Biol 8:497–501

    Google Scholar 

  • McCoy MS, Toole JJ, Cunningham JM, Chang EH, Lowy DR, Weinberg RA (1984) Characterization of human colon/lung carcinoma oncogene. Mol Cell Biol 4:79–81

    Google Scholar 

  • Miller AD, Curran T, Verma IM (1984) c-fos protein can induce cellular transformation: a novel mechanism of activation of a cellular oncogene. Cell 36:51–60

    Google Scholar 

  • Müller R, Bravo R, Burckhardt J (1983) Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 312:716–720

    Google Scholar 

  • Murray MJ, Cunningham JM, Parada LF, Dautry F, Lebowitz P, Weinberg RA (1983) The HL-60 transforming sequence: aras oncogene coexisting with alteredmyc genes in hematopoietic tumors. Cell 33:749–757

    Google Scholar 

  • Nau MM, Burke J, Brooks J, Battey J, Sausville E, Gazdar AF, Kirsch JR, McBride DW, Bertness K, Hollis GF, Minna JD (1985) L-myc a newmyc related gene amplified and expressed in human small cell lung cancer. Nature 318:69–73

    Google Scholar 

  • Nau MM, Brooks BJ, Carney DN, Gazdar AF, Battey JF, Sausville EA, Minna JD (1986) Human small cell lung cancers with aplification and expression of the N-myc gene. Proc Natl Acad Sci USA 83:1092–1096

    Google Scholar 

  • Orkin SH, Goldman DS, Sallan SE (1984) Development of homozygosity for chromosome 11p markers in Wilms' tumour. Nature 309:172–174

    Google Scholar 

  • Pelicci PH, Lanfrancone L, Brathwaite MD, Wolman SR, Dalla-Favera R (1984) Amplification of the c-myb oncogene in a case of human acute myelogenous leukemia. Science 224:1117–1121

    Google Scholar 

  • Prehn J, Mercola M, Calame K (1984) Translocation affects normal c-myc promoter usage and activates fifteen tryptic c-myc transcription starts in plasmocytoma M603. Nucleic Acids Res 12:8987–9007

    Google Scholar 

  • Pulciani S, Santos E, Lauver AV, Long LK, Aaronson SA, Barbacid M (1982) Oncogenes in solid human tumours. Nature 300:539–542

    Google Scholar 

  • Rapp UR, Cleveland JL, Storm S (1986) Oncogenes: clinical relevance. In: Modern trend in human leukemia VII. Haematology and blood transfusion. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Reynolds AB, Vila J, Lansing TJ Potts WM, Weber MJ, Parsons JT (1987) Activation of the oncogenic potential of the avian cellularsrc protein by specific structural alteration of the carboxy terminus. EMBO J 6:2359–2364

    Google Scholar 

  • Robbins KC, Devare SG, Aaronson SA (1981) Molecular cloning of integrated simian sarcoma virus: genome organization of infectious DNS clones. Proc Natl Acad SCI USA 78:2918–2922

    Google Scholar 

  • Rodenhuis S, van de Wetering M, Mooi WJ, Evers SG, van Zandwijk N, Bos JL (1987) mutational activation of the K-ras oncogene: a possible pathogenetic factor in adenocarcinoma of the lung. N Engl J Med 317:929–935

    Google Scholar 

  • Rodenhuis S, Slebos RJC, Boot AJM, Evers SG, Mooi WJ, Wagenaar SSc, van Bodegom PCh, Bos Jl (1988) Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res 48:5738–5741

    Google Scholar 

  • Saksela K, Bergh J, Lehto VP, Nilsson K, Alitalo K (1985) Amplification of the c-myc oncogene in a subpopulation of human small cell lung cancer. Cancer Res 45:1823–1827

    Google Scholar 

  • Santos E, Martin-Zanca D, Reddy EP, Pierotti MA, Della Porta G, Barbacid M (1984) Malignant activation of a Ki-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science 223:661–664

    Google Scholar 

  • Schwab M, Alitalo K, Klempmauer KH, Varmus HE, Bishop JM, Gilbert F, Brodeur G, Goldstein M, Trent J (1983) Amplified DNA with limited homology tomyc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumor. Nature 305:245–248

    Google Scholar 

  • Sherr CJ, Fedele LA, Oskarsson M, Maizel J, Woude GV (1980) Molecular cloning of Shyder-Theilen feline leukemia and sarcoma viruses: comparative studies of feline sarcoma virus with its natural helper virus and with Moloney murine sarcoma virus. J Virol 34:200–212

    Google Scholar 

  • Sherwin SA, Minna JD, Gazdar AF, Todaro GJ (1981) Expression of epidermal and nerve growth factor receptors and soft agar growth factor production by human lung cancer cells. Cancer Res 41:3538–3542

    Google Scholar 

  • Slamon DJ, Kernion JB, Verma JM, Cline MJ (1984) Expression of cellular oncogenes in human malignancies. Science 224:256–262

    Google Scholar 

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Google Scholar 

  • Smith GE, Summers MD (1980) The bidirectional transfer of DNA and RNA to nitrocellulose or diazobenzyloxymethyl-paper. Anal Biochem 109:123–129

    Google Scholar 

  • Vennström B, Fanshier L, Moscovici C, Bishop JM (1980) Molecular cloning of the avian erythroblastosis virus genome and recovery of oncogenic virus by transfection of chicken cells. J Virol 36:575–585

    Google Scholar 

  • Watson R, Oskarsson M, Vande Wonde GF (1982) Human DNA sequence homologous to the transforming gene (mos) of moloney murine sarcoma virus. Proc Natl Acad Sci USA 79:4078–4082

    Google Scholar 

  • Yuasa Y, Srivastava SK, Dunn CY, Rhim JS, Reddy EP, Aaronson SA (1983) Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene. Nature 303:775–779

    Google Scholar 

  • Yuasa Y, Gol RA, Chang A, Chiu JM, Reddy EP, Tronick SR, Aaronson SA (1984) Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells. Proc Natl Acad Sci USA 81:3670–3674

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Haematology/Oncology, Philipps-University Marburg, D-3550, Marburg, Federal Republic of Germany

    P. E. Kiefer, B. Wegmann, M. Bacher, C. Erbil, H. Heidtmann & K. Havemann

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  1. P. E. Kiefer
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  2. B. Wegmann
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  3. M. Bacher
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  4. C. Erbil
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  5. H. Heidtmann
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  6. K. Havemann
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Kiefer, P.E., Wegmann, B., Bacher, M. et al. Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines. J Cancer Res Clin Oncol 116, 29–37 (1990). https://doi.org/10.1007/BF01612637

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