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Cellular and Molecular Studies of Growth, Differentiation and Neoplastic Transformation of Human Bronchial Epithelial Cells in Vitro

  • Curtis C. Harris
  • Roger R. Reddel
  • Yang Ke
  • Andrea Pfeiffer
  • George Mark
  • Tohru Masui
  • George Yoakum
  • Brenda I. Gerwin
  • Paul Amstad
  • John F. Lechner

Abstract

Normal human cells in vitro appear to retain many normal phenotypic properties, remain diploid, eventually undergo senescence and rarely, if ever “spontaneously” transform to malignant cells. Retained properties may include synthesis of classes of proteins associated with specific cell types such as collagens, keratins, or melanin; responsiveness to hormones; and antigenic specificity. In addition, human cells with abnormal phenotypes such as either enzymatic deficits or malignant properties frequently maintain these phenotype in vitro. Human cells cultured in vitro have thus proven to be extremely useful to scientists studying the molecular and biochemical aspects of human carcinogenesis. Such studies have been facilitated by the recent development of improved methods for culturing normal human epithelial tissues and cells1. Chemically defined media have been developed for culturing many of these tissues and cells from normal organs, including those with a high rate of cancer in humans. Serum-free media have several advantages in studies of cultured human cells, including: (a) less experimental variability compared to serum-containing media; (b) selective growth conditions for normal cells of different types (e.g. epithelial versus fibroblastic) or for normal versus malignant cells; (c) ease of identification of growth factors, inhibitors of growth, and inducers of differentiation; and (d) ease of isolating and analyzing secreted cellular products. Advances in cell biology, including the delineation of biochemical and morphological markers of specific cell types, have also facilitated the identification of cells in vitro (including keratins as markers for epithelial cells and collagen types I and III for identifying fibroblasts). These advances have created experimental approaches to answering critical questions in human cell carcinogenesis1,2.

Keywords

Bronchial Epithelial Cell Neoplastic Transformation Human Bronchial Epithelial Cell Squamous Differentiation Normal Human Bronchial Epithelial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    C. C. Harris, Human tissues, and cells in carcinogenesis research, Cancer Res. 47:1 (1987).PubMedGoogle Scholar
  2. 2.
    D. E. Brash, G. E. Mark, M. P. Farrell and C. C. Harris, Overview of human cells in genetic research: Altered phenotypes in human cells caused by transferred genes, Somatic Cell and Mol. Genetics 13:429 (1987).CrossRefGoogle Scholar
  3. 3.
    S. H. Yuspa, Alterations in epidermal differentiation in skin carcinogenesis, in: “Interrelationship among Aging, Cancer and Differentiation”, B. Pullman, ed., D. Reidel Publishing, New York (1985).Google Scholar
  4. 4.
    M. B. Sporn and A. B. Roberts, Autocrine growth factors and cancer, Nature (Lond) 313:747 (1985).CrossRefGoogle Scholar
  5. 5.
    T. W. Moody, C. B. Pert, A. F. Gadzar, D. N. Carney and J. D. Minna, High levels of intracellular bombesin characterize human small-cell carcinoma, Science (Wash. P.C.) 214:1246 (1981).CrossRefGoogle Scholar
  6. 6.
    B. F. Trump, T. Wilson and C. C. Harris, Recent progress in the pathology of lung neoplasms, in: “Lung Cancer”, S. Ishikawa, Y. Hayata, and K. Suematsu, eds., Excerpta, Amsterdam (1982).Google Scholar
  7. 7.
    F. Cuttitta, D. N. Carney, J. Mulshine, T. W. Moody, J. Fedorko, A. Fischler and J. D. Minna, Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer, Nature (Lond) 316:823 (1985).CrossRefGoogle Scholar
  8. 8.
    J. C. Willey, J. F. Lechner and C. C. Harris, Bombesin and the C-terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal human bronchial epithelial cells, Exp. Cell. Res. 153:245 (1984).PubMedCrossRefGoogle Scholar
  9. 9.
    C. C. Harris, G. H. Yoakum, J. F. Lechner, J. C. Willey, T. Masui, B. Gerwin, S. Schlegel and G. Mark, Growth, differentiation and neoplastic transformation of human bronchial epithelial cells, in: “Biochemical and Molecular Epidemiology of Cancer”, C. C. Harris, ed., Alan R. Liss, New York (1986).Google Scholar
  10. 10.
    E. A. Friedman, Differential response of premalignant epithelial cell classes to phorbol ester tumor promoters and to deoxycholic acid, Cancer Res. 41:4588 (1981).PubMedGoogle Scholar
  11. 11.
    R. Reddel, K. Yang, B. I. Gerwin, M. McMenamin, J. F. Lechner, R. Hsu, D; E. Brash, J. B. Park, J. S. Rhim and C. C. Harris, 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, (in press).Google Scholar
  12. 12.
    J. S. Rhim, G. Jay, P. Arnstein, F. M. Price, K. K. Sanford and S. A. Aaronson, Neoplastic transformation of human epidermal keratinocytes by AD12-SV-40 and Kirsten sarcoma viruses, Science (Wash. P.C.) 227:1250 (1985).CrossRefGoogle Scholar
  13. 13.
    F. L. Graham, J. Smiley, W. C. Russell and R. Nairn, Characteristics of a human cell line trasformed by DNA from human adenovirus type 5, J. Gen. Virol. 36:59 (1977).PubMedCrossRefGoogle Scholar
  14. 14.
    G. H. Yoakum, J. F. Lechner, E. Gabrielson, B. E. Korba, L. Malan-Shibley, J. C. Willey, M. G. Valerio, A. K. M. Shamsuddin, B. F. Trump and C. C. Harris, Transformation of human bronchial epithelial cells transfected by Harvey ras oncogene, Science 227:1174 (1985).PubMedCrossRefGoogle Scholar
  15. 15.
    P. Boukamp, E. J. Stanbridge, P. A. Cerutti and N. E. Fusenig, Malignant transformation of 2 human-skin keratinocyte lines by Harvey-ras oncogene, J. Invest. Dermatol. 87:131 (1986).Google Scholar
  16. 16.
    N. E. Fusenig, P. Boukamp, D. Breitkreutz, S. Karjetta and R. Dzarlieva-Petrusevska, Oncogenes and malignant transformation of human keratinocytes, Abstract of Second International Conf. on Anticarcinogenesis and Radiation Protection, Gaithersburg, Maryland (1987).Google Scholar
  17. 17.
    J. S. Rhim, J. Fujita, P. Arnstein and A. A. Aaronson, Neoplastic conversion of human epidermal keratinocytes by adenovirus 12-SV-40 virus and chemical carcinogens, Science (Wash. P.C.) 232:385 (1986).CrossRefGoogle Scholar
  18. 18.
    D. J. Kessler, C. A. Heilman, J. Cossman, R. T. Maguire and S. S. Thorgeirsson, Transformation of Epstein-Barr virus immortalized human B-cells by chemical carcinogens, Cancer Res. 47:527 (1987).PubMedGoogle Scholar
  19. 19.
    P. C. Nowell, Mechanisms of tumor progression, Cancer Res. 46:2203 (1986).PubMedGoogle Scholar
  20. 20.
    D. A. Spandidos and N. M. Wilkie, Malignant transformation of early passage rodent cells by a single mutated human oncogene, Nature (Lond.) 310:469 (1984).CrossRefGoogle Scholar
  21. 21.
    R. Sager, K. Tanaka, C. C. Lau, Y. Ebina and A. Anisowicz, Resistance of human cells to tumorigenesis induced by cloned transforming genes, Proc. Natl. Acad. Sci. USA 80:7601 (1983).PubMedCrossRefGoogle Scholar
  22. 22.
    B. R. Franza, K. Maruyama, J. I. Garrels and H. E. Ruley, In vitro establishment is not sufficient prerequisite for transformation by activated ras oncogenes, Cell 44:409 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Curtis C. Harris
    • 1
  • Roger R. Reddel
    • 1
  • Yang Ke
    • 1
  • Andrea Pfeiffer
    • 1
  • George Mark
    • 1
  • Tohru Masui
    • 1
  • George Yoakum
    • 1
  • Brenda I. Gerwin
    • 1
  • Paul Amstad
    • 1
  • John F. Lechner
    • 1
  1. 1.Laboratory of Human Carcinogenesis, Division of Cancer EtiologyNational Cancer InstituteBethesdaUSA

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