Constitutive and Induced Expression of Heat Shock Proteins During Liver Carcinogenesis and in Hepatomas

  • Gaetano Cairo
  • Emilia Rappocciolo
  • Lorenza Tacchini
  • Lidia Bardella
  • Luisa Schiaffonati
  • Aldo Bernelli-Zazzera


Exposure of cells to heat or other stresses1 induces in the chromosomes the appearance of a new set of puffs2 and causes changes in gene structure and regulation that finally lead to the activation of synthesis of a distinct group of proteins. These proteins, known historically as heat-shock proteins (hsps), are now often referred to as stress proteins3–5. The best evolutionarily conserved heat-shock protein, hsp 70, is coded by a multigene family whose members respond in different ways to temperature and are subject to different regulatory mechanisms; the heat-inducible and constitutive proteins have sometimes been confused4 At least one of the members of the hsp 70 group is also growth-regulated6–7 and the activity of the corresponding gene is induced by viral and cellular oncogenes8,10. In previous studies we have examined the synthesis of hsp in injured liver cells11 and in some hepatomas of different growth rates12, and have shown that in these tumours hsp 89 and hsp 70 are expressed constitutively, while induction by heat, at least in the case of hsp 70, is progressively reduced from the slow to the fast-growing hepatomas13. Later on we became aware of the fact that hsc 73, the major heat-shock related protein, rather than hsp 70 itself, is the main constitutively synthesized protein in unstressed cells; moreover recent data showed that hsc 73 is expressed at higher level in transformed cells than in their non-transformed counterparts14. In the present paper we report the results of an investigation with a probe for hsc 73, which became recently available to us, on the constitutive expression of hsc 73 gene in liver cells submitted to a multistep carcinogenic treatment and in transplantable hepatomas, both solid and in ascitic form, of various growth rates. The main purpose of the investigation was to see if the constitutive expression of hsc 73 is an event occurring during the carcinogenic treatment, presumably associated with initiation and/or promotion, or a relatively late outcome during the growth of the established tumour, presumably associated with tumor progression.


Heat Shock Gene Liver Carcinogenesis Carbamyl Phosphate Ascitic Form Cellular Oncogenes8 
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  1. 1.
    M. J. Schlesinger, M. Ashburner and A. Tissieres, “Heat shock. From Bacteria to Man”, Cold Spring Harbor Laboratory, Cold Spring Harbor (1982).Google Scholar
  2. 2.
    F. Ritossa, A new puffing pattern induced by temperature shock and DNP in Drosophilia, Experientia 18:571 (1962).CrossRefGoogle Scholar
  3. 3.
    R. H. Burdon, Heat shock and the heat shock proteins, Biochem. J. 240:313 (1986).PubMedGoogle Scholar
  4. 4.
    S. Lindquist, The heat shock response, Ann. Rev. Biochem. 55:1151 (1986).PubMedCrossRefGoogle Scholar
  5. 5.
    J. R. Subjeck and T-T. Shyy, Stress protein systems of mammalian cells, Am. J. Physiol. 250: c1 (1986).PubMedGoogle Scholar
  6. 6.
    BN. J. Wu and R. I. Morimoto, Transcription of the human hsp 70 gene is induced by serum stimulation, Proc. Natl. Acad. Sci. USA 82:6070 (1985).PubMedCrossRefGoogle Scholar
  7. 7.
    H. T. Kao, O. Capasso, N. Heintz and J. R. Nevins, Cell cycle control of the human hsp 70 gene: implications for the role of a cellular E1A-like function, Mol. Cell. Biol. 5:628 (1985).PubMedGoogle Scholar
  8. 8.
    J. R. Nevins, Induction of the synthesis of 70.000 dalton mammalian heat shock protein by the adenovirus E1A gene product, Cell 29:913 (1982).PubMedCrossRefGoogle Scholar
  9. 9.
    M. J. Imperiale, H. T. Kao, L. T. Feldman, J. R. Nevins and S. Strickland, Common control of the heat shock gene and early adenovirus genes: evidence for a cellular E1A-like activity, Mol. Cell. Biol. 4:867 (1984).PubMedGoogle Scholar
  10. 10.
    R. E. Kingston, A. S. Baldwin, Jr. and P. A. Sharp, Regulation of heat shock gene 70 expression by c-myc, Nature 312:280 (1984).PubMedCrossRefGoogle Scholar
  11. 11.
    G. Cairo, L. Bardella, L. Schiaffonati and A. Bernelli-Zazzera, Synthesis of heat shock proteins in rat liver after ischemia and hyperthermia, Hepatology 5:357 (1985).PubMedCrossRefGoogle Scholar
  12. 12.
    L. Bardella, L. Schiaffonati, G. Cairo and A. Bernelli-Zazzera, Synthesis of heat-shock proteins in liver and hepatomas of different growth rate, Biochem. Soc. Trans. 14:974 (1986).Google Scholar
  13. 13.
    L. Bardella, L. Schiaffonati, G. Cairo and A. Bernelli-Zazzera, Heatshock proteins and mRNAs in liver and hepatoma, Br. J. Cancer 55:643 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    O. Pinhasi-Kimhi, D. Michalovitz, A. Ben-Zeev and M. Oren, Specific interaction between the p53 cellular tumor antigene and major heat shock proteins, Nature 320:182 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    D. B. Solt and E. Farber, New Principle for the analysis of chemical carcinogenesis, Nature 263:701 (1976).CrossRefGoogle Scholar
  16. 16.
    Y. Raymond and G. C. Shore, The precursor for carbamyl phosphate synthetase is transported to mitochondria via a cytosolic route, J. Biol. Chem. 19:9335 (1979).Google Scholar
  17. 17.
    G. Cairo, L. Bardella, L. Schiaffonati, P. Arosio, S. Levi and A. Bernelli-Zazzera, Multiple mechanisms of iron-induced ferritin synthesis in HeLa cells, Biochem. Biophis. Res. Commun. 133:314 (1985).CrossRefGoogle Scholar
  18. 18.
    G. Cairo, P. Vezzoni, L. Bardella, E. Rappocciolo, S. Levi, P. Arosio and A. Bernelli-Zazzera, Regulation of ferritin synthesis in malignant and non-malignant lymphoid cells, Biochem. Biophys. Res. Commun. 139:652 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    P. K. Sorger and H. R. B. Pelham, Cloning and expression of a gene incoding hsc 73, the major hsp 70-like protein in unstressed rat cells EMBO J. 6:993 (1987).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Gaetano Cairo
    • 1
  • Emilia Rappocciolo
    • 1
  • Lorenza Tacchini
    • 1
  • Lidia Bardella
    • 1
  • Luisa Schiaffonati
    • 1
  • Aldo Bernelli-Zazzera
    • 1
  1. 1.Istituto di Patologia Generale dell’Università degli StudiCentro di Studio sulla Patologia Cellulare del CNRMilanoItaly

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