Abstract
Carcinogenesis is a multistage process involving both genetic and epigenetic aberrations. Activation of proto-oncogenes and/or inactivation of tumor suppressor genes may occur in an early stage of carcinogenesis, i.e., tumor initiation, as well as in the later stages e.g., tumor conversion and progression (Fig. 1). For example, activation of Ki-ras by base substitution mutations is an early event in human colon carcinogenesis (Vogelstein et al., 1988), whereas amplification of N-myc is associated with the tumor progression stage of human neuroblastoma (Brodeur et al., 1987). In the inherited form of retinoblastoma, a defective tumor suppressor gene, Rb-1, is found in the germline DNA and the second Rb-1 allele is inactivated most frequently by deletion or recombinational mechanisms during the initia1 stages of carcinogenesis (Knudson, 1985; Hansen et al., 1985; Cavenee et al., 1986; Friend et al., 1986; Fung et al., 1987). In contrast, the inactivation by somatic mutation of both alleles of the p53 gene appears to occur during tumor progression of human carcinomas of the colon (Baker et al., 1989), breast and lung (Nigro et al., 1989).
To Whom Correspondence Should Be Addressed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Amstad, P., Reddel, R. R., Pfeifer, A., Malan-Shibley, L., Mark, G. E., and Harris, C. C., 1988, Neoplastic transformation of a human bronchial epithelial cell line by a recombinant retrovirus encoding viral harvey ras, Mol.Carcinogenesis, 1: 151.
Baker, S. J., Fearon, E. R., Nigro, J. M., Hamilton, S. R., Preisinger, A. C., Jessup, J. M., Van Tuinen, P., Ledbetter, D. H., Barker, D. F., and Nakamura, Y., 1989, Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas, Science, 244: 217.
Bondy, G. P., Wilson, S., and Chambers, A. F., 1985, Experimental metastatic ability of H-ras-transformed NIH3T3 cells, Cancer Res., 45: 6005.
Bonfil, R. D., Reddel, R. R., Ura, H., Reich, R., Fridman, R., Harris, C. C., and Klein-Szanto, A. J., 1989, Invasive and metastatic potential of a v-Ha-ras-transformed human bronchial epithelial cell line, J.Natl.Cancer Inst., 81: 587.
Brauch, H., Johnson, B., Hovis, J., Yano, T., Gazdar, A. F., Pettengill, O. S., Graziano, S. L., Sorenson, G. D., Poiesz, B. J., Minna, J., Linehan, M., and Zbar, B., 1987, Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung, N.Engl.J.Med., 317: 1109.
Brodeur, G. M., Hayes, F. A., Green, A. A., Casper, J. T., Wasson, J., Wallach, S., and Seeger, R. C., 1987, Consistent N-myc copy number in simultaneous or consecutive neuroblastoma samples from sixty individual patients, Cancer Res., 47: 4248.
Byrd, P. J., Grand, R. J., and Gallimore, P. H., 1988, Differential transformation of primary human embryo retinal cells by adenovirus E1 regions and combinations of E1A + ras, Oncogene, 2: 477.
Carney, D. N., Edgell, C. J., Gazdar, A. F., and Minna, J. D., 1979, Suppression of malignancy in human lung cancer (A549/8) times mous? fibroblast (3P3–4E) somatic cell hybrids, J.Natl.Cancer Inst., 69: 411.
Cavenee, W. K., Murphree, A. L., Shull, M. M., Benedict, W. F., Sparkes, R. S., Kock, E., and Nordenskjold, M., 1986, Prediction of familial predisposition to retinoblastoma, N.Engl.J.Med., 314: 1201.
Clark, R., Stampfer, M. R., Milley, R., O’Rourke, E., Walen, K. H., Kriegler, M., Kopplin, J., and McCormick, F., 1988, Transformation of human mammary epithelial cells by oncogenic retroviruses, Cancer Res., 48: 4689.
Der, C. J., Krontiris, T. G., and Cooper, G. M., 1982, Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses, Proc.Natl.Acad.Sci.USA., 79: 3637.
Doll, R., 1985, Cancer: a world wide perspective, in: “Biochemical and Molecular Epidemiology of Cancer,” C. C. Harris, ed., Alan R. Liss, Inc., New York.
Fasano, O., Aldrich, T., Tamanoi, F., Taparowsky, E., Furth, M., and Wigler, M., 1984, Analysis of the transforming potential of the human H-ras gene by random mutagenesis, Proc.Natl.Acad.Sci.USA, 81: 4008.
Fearon, E. R., Vogelstein, B., and Feinberg, A. P., 1984, Somatic deletion and duplication of genes on chromosome 11 in Wilms’ tumours. Nature, 309: 176.
Fearon, E. R., Feinberg, A. P., Hamilton, S. H., and Vogelstein, B., 1985, Loss of genes on the short arm of chromosome 11 in bladder cancer, Nature, 318: 377.
Fearon, E. R., Hamilton, S. R., and Vogelstein, B., 1987, Clonal analysis of human colorectal tumors, Science, 238: 193.
Fraumeni, J. F. Jr., and Blot, W. J., 1982, Lung and pleura, in: “Cancer Epidemiology and Prevention,” D. Schottenfeld, and J. F. Fraumeni, eds., W.R. Saunders Co., Philadelphia.
Friend, S. H., Bernards, R., Rogelj, S., Weinberg, R. A., Rapaport, J. M., Albert, D. M., and Dryja, T. P., 1986, A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma, Nature, 323: 643.
Fung, Y. K., Murphree, A. L., T’Ang, A., Qian, J., Hinrichs, S. H., and Benedict, W. F., 1987, Structural evidence for the authenticity of the human retinoblastoma gene, Science, 236: 1657.
Graziano, S. L., Cowan, B. Y., Carney, D. N., Bryke, C. R., Hitter, N. S., Johnson, B. E., Mark, G. E., Planas, A. T., Catino, J. J., Comis, R. L., and Poiesz, B. J., 1987, Small cell lung cancer cell line derived from a primary tumor with a characteristic deletion of 3p, Cancer Res., 47: 2148.
Gu, J., Linnoila, R. I., Seibel, N. L., Gazdar, A. F., Minna, J. D., Brooks, B. J. Jr., Hollis, G. F., and Kirsch, I. R., 1988, A study of myc-related gene expression in small cell lung cancer by in situ hybridization, Am.J.Pathol., 132: 13.
Guerrero, I., Calzada, P., Mayer, A., and Pellicer, A., 1984, A molecular approach to leukemogenesis: mouse lymphomas contain an activated c-ras oncogene, Proc.Natl.Acad.Sci.USA., 81: 202.
Gusella, J. F., 1986, DNA polymorphism and human disease, Annu.Rev.Biochem., 55: 831.
Hansen, M. F., and Cavenee, W. K., 1987, Genetics of cancer predisposition, Cancer Res., 47: 5518.
Hansen, M. F., Koufos, A., Gallie, B. L., Phillips, R. A., Fodstad, O., Brogger, A., Gedde-Dahl, T., and Cavenee, W. K., 1985, Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition, Proc.Natl.Acad.Sci.USA., 82: 6216.
Harbour, J. W., Lai, S. L., Whang-Peng, J., Gazdar, A. F., Minna, J. D., and Kaye, F. J., 1988, Abnormalities in structure and expression of the human retinoblastoma gene in SCLC, Science, 241: 353.
Harris, C. C., 1982, Respiratory carcinogenesis and cancer epidemiology, in: “Lung Cancer: Clinical Diagnosis and Treatment,” M. Straus, ed., Grune and Stratton, New York.
Harris, C. C., 1987, Human tissues and cells in carcinogenesis research, Cancer Res., 47: 1.
Harris, H., 1988, The analysis of malignancy by cell fusion: the position in 1988, Cancer Res., 48: 3302.
Huang, H. J., Yee, J. K., Shew, J. Y., Chen, P. L., Bookstein, R., Friedmann, T., Lee, E. Y., and Lee, W. H., 1988, Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells, Science, 242: 1563.
Kaelbling, M., and Klinger, H. P., 1986, Suppression of tumorigenicity in somatic cell hybrids. III Cosegregation of human chromosome 11 of a normal cell and suppression of tumorigenicity in intraspecies hybrids of normal diploid x malignant cells, Cytogenet.Cell Genet., 41: 65.
Kaighn, M. E., Gabrielson, E. W., Iman, D. S., Pauls, E. A., and Harris, C. C., 1989, Suppression of tumorigenicity of a human lung carcinoma line by nontumorigenic bronchial epithelial cells in somatic cell hybrids, Proc.Am.Assoc.Cancer Res., 30: 445.
Kasid, A., Lippman, M. E., Papageorge, A. G., Lowy, D. R., and Gelmann, E. P., 1985, Transfection of v-rasH DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity, Science, 228: 725.
Kasid, U., Pfeifer, A., Weichselbaum, R. R., Dritschilo, A., and Mark, G. E., 1987, The raf oncogene is associated with a radiation-resistant human laryngeal cancer, Science, 237: 1039.
Kasid, U., Pfeifer, A., Weichselbaum, R. R., Dritschilo, A., and Mark, G. E., 1989, Effect of anti-sense c-raf-1 on tumorigenicity and radiation sensitivity of human squamous carcinoma, Science, 243: 1354.
Ke, Y., Reddel, R. R., Gerwin, B. I., Miyashita, M., McMenamin, M. G., Lechner, J. F., and Harris, C. C., 1988, Human bronchial epithelial cells with integrated SV40 virus T antigen genes retain the ability to undergo squamous differentiation, Differentiation, 38: 60.
Knudson, A. G. Jr., 1985, Hereditary cancer, oncogenes, and antioncogenes, Cancer Res., 45: 1437.
Kok, K., Osinga, J., Carritt, B., Davis, M. B., Van der Hout, A. H., Van der Veen, A. Y., Landsvater, R. M., de Leij, L. F., Berendsen, H. H., Postmus, P. E., Poppema, S., and Buys, C. H., 1987, Deletion of a DNA sequence at the chromosomal region 3p21 in all major types of lung cancer, Nature, 330: 578.
Koufos, A., Hansen, M. F., Lampkin, B. C., Workman, M. L., Copeland, N. G., Jenkins, N. A., and Cavenee, W. K., 1984, Loss of alleles at loci on human chromosome 11 during genesis of Wilms’ tumour, Nature, 309: 170.
Kraevskii, A., 1979, Classification and pathological anatomy of lung cancer, in: “Cancer of the Lung,” B. E. Peterson, ed., PSG Publishing Co., Massachusetts.
Krystal, G., Birrer, M. J., Way, J., Nau, M. M., Sausville, E., Thompson, C., Minna, J. D., and Battey, J. F., 1988, Multiple mechanisms for transcriptional regulation of the myc gene family in small-cell lung cancer, Mol.Cell Biol., 8: 3373.
Lechner, J. F., McClendon, I. A., LaVeck, M. A., Shamsuddin, A. K. M., and Harris, C. C., 1983, Differential control by platelet factors of squamous differentiation in normal and malignant human bronchial epithelial cells, Cancer Res., 43: 5915.
Lechner, J. F., 1984a, Inhibition of cell growth by serum, In Vitro Monograph, 5: 80.
Lechner, J. F., Haugen, A., McClendon, I. A., and Shamsuddin, A. K. M., 1984b, Induction of squamous differentiation of normal human bronchial epithelial cells by small amounts of serum, Differentiation, 25: 229.
Lee, W. H., Bookstein, R., Hong, F., Young, L. J., Shew, J. Y., and Lee, E. Y., 1987, Human retinoblastoma susceptibility gene: cloning, identification, and sequence, Science, 235: 1394.
McMenamin, M. G., Iman, D. S., Stanbridge, E. J., Shows, T. B., and Harris, C. C., 1989, Tumor suppressor activity of microcell transferred human chromosomes in lung carcinoma cells, Proc.Am.Assoc.Cancer Res., 30: 189.
Modali, R., Lehman, T. A., Weston, A., Romano, J., Appella, E., Vogelstein, B., and Harris, C. C., 1989, Mutations in the p53 gene in human lung carcinoma cell lines, Am.Soc.Hum.Genet. In press.
Namba, M., Nishitani, K., Fukushima, F., Kimoto, T., and Nose, K., 1985, Multistep process of neoplastic transformation of normal human fibroblasts by 60Co gamma rays and Harvey sarcoma viruses, Int.J.Cancer, 37: 419.
Naylor, S. L., Johnson, B. E., Minna, J. D., and Sakaguchi, A. Y., 1987, Loss of heterozygosity of chromosome 3p markers in small- cell lung cancer, Nature, 329: 451.
Nigro, J. M., Baker, S. J., Preisinger, A. C., Jessup, J. M., Hostetter, R., Cleary, K., Bigner, S. H., Davidson, N., Baylin, S., Devilee, P., Glover, T., Collins F. S., Weston, A., Modali, R., Harris, C. C., and Vogelstein, B., 1989, p53 gene mutations occur in diverse human tumor types, Nature, in press.
O’Brien, W., Stenman, G., and Sager, R., 1986, Suppression of tumor growth by senescence in virally transformed human fibroblasts, Proc.Natl.Acad.Sci.USA., 83: 8659.
Orkin, S. H., Goldman, D. S., and Sallan, S. E., 1984, Development of homozygosity for chromosome 11p markers in Wilms’ tumour, Nature, 309: 172.
Pater, A., and Pater, M. M., 1986, Transformation of primary human embryonic kidney cells to anchorage independence by a combination of BK virus DNA and the Harvey-ras oncogene, J.Virol., 58: 680.
Pfeifer, A., Mark, G. E., Malan-Shibley, L., Graziano, S. L., Amstad, P., and Harris, C. C., 1989, Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of SV40 T-antigen immortalized human bronchial epithelial cells, Proc.Natl.Acad.Sci.USA. In press.
Pulciani, S., Santos, E., Lauver, A. V., Long, L. K., Aaronson, S. A., and Barbacid, M., 1982, Oncogenes in solid human tumours, Nature, 300: 539.
Rapp, U. R., Huleihel, M., Pawson, T., Linnoila, I., Minna, J. D., Heidecker, G., Cleveland, J. L., Beck, T., Forchhammer, J., and Storm, S. M., 1988, Role of raf oncogenes in lung carcinogenesis, Lung Cancer, 4: 162.
Reddel, R. R., Ke, Y., Kaighn, M. E., Malan-Shibley, L., Lechner, J. F., Rhim, J. S., and Harris, C. C., 1988a, Human bronchial epithelial cells neoplastically transformed by v-Ki-ras: Altered response to inducers of terminal squamous differentiation, Oncogene Res., 3: 401.
Reddel, R. R., Ke, Y., Gerwin, B. I., McMenamin, M. G., Lechner, J. F., Su, R. T., Brash, D. E., Park, J. B., Rhim, J. S., and Harris, C. C., 1988b, Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes, Cancer Res., 48: 1904.
Reeve, A. E., Housiaux, P. J., Gardner, R. J., Chewings, W. E., Grindley, R. M., and Millow, L. J., 1984, Loss of a Harvey ras allele in sporadic Wilms’ tumour, Nature, 309: 174.
Reznikoff, C. A., Loretz, L. J., Christian, B. J., Wu, S. Q., and Meisner, L. F., 1988, Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene, Carcinogenesis, 9: 1427.
Rhim, J. S., Trimmer, R., Arnstein, P., and Huebner, R. J., 1981, Neoplastic transformation of chimpanzee cells induced by adenovirus type 12--simian virus 40 hybrid virus, Proc.Natl.Acad.Sci.USA., 78: 313.
Rodenhuis, S., Van de Wetering, M. L., Mooi, W. J., Evers, S. G., Van Zandwijk, N., and Bos, J. L., 1987, Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung, N.Engl.J.Med., 317: 929.
Romano, J. W., Ehrhart, J. C., Duthu, A., Kim, C. M., Appella, E., and May, P., 1989, Identification and characterization of a p53 gene mutation in a human osteosarcoma cell line, Oncogene. In press.
Sager, R., 1985, Genetic suppression of tumor formation, Adv.Cancer Res., 44: 43.
Santos, E., Martin-Zanca, D., Reddy, E. P., Pierotti, M. A., Della Porta, G., and Barbacid, M., 1984, Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient, Science, 223: 661.
Saxon, P. J., Srivatsan, E. S., and Stanbridge, E. J., 1986, Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells, EMBO J., 5: 3461.
Scott, R. E., and Florine, D. L., 1982, Cell cycle models for the aberrant coupling of growth arrest and differentiation in hyperplasia, metaplasia, and neoplasia, Am.J.Pathol., 107: 342.
Scrable, H. J., Witte, D. P., Lampkin, B. C., and Cavenee, W. K., 1987, Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping, Nature, 329: 645.
Seremetis, S., Inghirami, G., Ferrero, D., Newcomb, E. W., Knowles, D. M., Dotto, G. P., and Dalla-Favera, R., 1989, Transformation and plasmacytoid differentiation of EBV-infected human B lymphoblasts by ras oncogenes, Science, 243: 660.
Shiraishi, M., Morinaga, S., Noguchi, M., Shimosato, Y., and Sekiya, T., 1987, Loss of genes on the short arm of chromosome 11 in human lung carcinomas, Jpn.J.Cancer Res., 78: 1302.
Slack, J. M., 1986, Epithelial metaplasia and the second anatomy, Lancet, 2: 268.
Smits, H. L., Floyd, E. E., and Jetten, A. M., 1987, Molecular cloning of gene sequences regulated during squamous differentiation of tracheal epithelial cells and controlled by retinoic acid, Mol.Cell Biol., 7: 4017.
Stanbridge, E. J., Der, C. J., Doersen, C. J., Nishimi, R. Y., Peehl, D. M., Weissman, B. E., and Wilkinson, J. E., 1982, Human cell hybrids: analysis of transformation and tumorigenicity, Science, 215: 252.
Suda, Y., Aizawa, S., Hirai, S., Inoue, T., Furuta, Y., Suzuki, M., Hirohashi, S., and Ikawa, Y., 1987, Driven by the same Ig enhancer and SV40 T promoter ras induced lung adenomatous tumors, myc induced pre-B cell lymphomas and SV40 large T gene a variety of tumors in transgenic mice, EMBO J., 6: 4055.
T’Ang, A., Varley, J. M., Chakraborty, S., Murphree, A. L., and Fung, Y. K., 1988, Structural rearrangement of the retinoblastoma gene in human breast carcinoma, Science, 242: 263.
Thompson, J. J., Zinsser, K. R., and Enterline, H. T., 1983, Barrett’s metaplasia and adenocarcinoma of the esophagus and gastroesophageal junction, Hum.Pathol., 14: 42.
Turleau, C., de Grouchy, J., Dufier, J. L., Phuc, L. H., Schmelck, P. H., Rappaport, R., Nihoul-Fekete, C., and Diebold, N., 1981, Aniridia, male pseudohermaphroditism, gonadoblastoma, mental retardation, and del 11p13, Hum.Genet., 57: 300.
Valenzuela, D. M., and Groffen, J., 1986, Four human carcinoma cell lines with novel mutations in position 12 of c-K-ras oncogene, Nucleic Acids Res., 14: 843.
Van Heyningen, V., Boyd, P. A., Seawright, A., Fletcher, J. M., Fantes, J. A., Buckton, K. E., Spowart, G., Porteous, D. J., Hill, R. E., Newton, M. S., and Hastie, N. D., 1985, Molecular analysis of chromosome 11 deletions in aniridia- Wilms tumor syndrome, Proc.Natl.Acad.Sci.USA, 82: 8592.
Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., Nakamura, Y., White, R., Smits, A. M., and Bos, J. L., 1988, Genetic alterations during colorectal-tumor development, N.Engl.J.Med., 319: 525.
Weissman, B. E., Saxon, P. J., Pasquale, S. R., Jones, G. R., Geiser, A. G., and Stanbridge, E. J., 1987, Introduction of a normal human chromosome 11 into a Wilms’ tumor cell line controls its tumorigenic expression, Science, 236: 175.
Weston, A., Willey, J. C., Modali, R., Sugimura, H., McDowell, E. M., Resau, J., Light, B., Haugen, A., Mann, D. L., Trump, B. F., and Harris, C. C., 1989, Differential DNA sequence deletions from chromosomes 3, 11, 13 and 17 in squamous cell carcinoma, large cell carcinoma and adenocarcinoma of the human lung, Proc.Natl.Acad.Sci.USA, 86: 5099.
Wille, J. J. Jr., Maercklein, P. B., and Scott, R. E., 1982, Neoplastic transformation and defective control of cell proliferation and differentiation, Cancer Res., 42: 5139.
Willey, J. C., Moser, C. E. Jr., Lechner, J. F., and Harris, C. C., 1984, Differential effects of 12–0-tetradecanoylphorbol-13-acetate on cultured normal and neoplastic human bronchial epithelial cells, Cancer Res., 44: 5124.
Winter, E., Yamamoto, F., Almoguera, C., and Perucho, M., 1985, A method to detect and characterize point mutations in transcribed genes: amplification and overexpression of the mutant c-Ki-ras allele in human tumor cells, Proc.Natl.Acad.Sci.USA., 82: 7575.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Plenum Press, New York
About this chapter
Cite this chapter
Harris, C.C. et al. (1990). Oncogenes and Tumor Suppressor Genes Involved in Human Lung Carcinogenesis. In: Sutherland, B.M., Woodhead, A.D. (eds) DNA Damage and Repair in Human Tissues. Basic Life Sciences, vol 53. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0637-5_29
Download citation
DOI: https://doi.org/10.1007/978-1-4613-0637-5_29
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-7903-7
Online ISBN: 978-1-4613-0637-5
eBook Packages: Springer Book Archive