Regulation of Protein Degradation in Neoplastic Cells

  • Franco M. Baccino
  • Riccardo Autelli
  • Gabriella Bonelli
  • Paola Costelli
  • Ciro Isidoro
  • Luciana Tessitore

Abstract

Changes in the overall rate of cell protein degradation (PD) were included by Hershko and co-workers in 19711 among the elements of the “pleiotypic response”, which was categorized as “positive” if associated with growth stimulation or “negative” if accompanying growth suppression. Protein turnover modulations were thus regarded as instrumental in effecting growth-phase transitions. In 1977 Warburton and Poole2 analyzed the relationship between cell growth and PD rates in tissue cultures exposed to serum deprivation or other manipulations. Moreover, in 1977 Gunn et al.3 reported that basal PD rates in various transformed cells were lower than in their normal counterparts, hypothesizing that a reduction in intracellular proteolysis could play a role in neoplastic growth. Since then, many methodological advances have been developed to analyze PD in tissues or cells, particularly in tissue cultures. Nevertheless, studies on the relationship between cell protein turnover rates and growth or neoplastic transformation have generally relied on experimental models not adequately defined in terms of growth properties and kinetics, not to mention the rather crude tools often used to elicit growth-phase transitions.

Keywords

Adenine Triglyceride Glucagon Thymidine Purine 

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References

  1. 1.
    A. Hershko, P. Mamont, R. Shields and G. M. Tomkins, Pleiotypic response, Nature 232:206 (1971).Google Scholar
  2. 2.
    M. J. Warburton and B. Poole, Effect of medium composition on protein degradation and DNA synthesis in rat embryo fibroblasts, Proc. Natl. Acad. Sci. USA 74:2427 (1977).PubMedCrossRefGoogle Scholar
  3. 3.
    J. M. Gunn, M. G. Clark, S. E. Knowles, M. F. Hopgood, and F. J. Ballard, Reduced rates of proteolysis in transformed cells, Nature 266:58 (1977)PubMedCrossRefGoogle Scholar
  4. 4.
    A. M. Spanier, W. A. Clark jr., and R. Zak, Replacement perfusion of cultured eucaryotic cells: a method for the accurate measurement of the rates of growth, protein synthesis, and protein turnover, J. Cell. Biochem. 26:67 (1984).CrossRefGoogle Scholar
  5. 5.
    F. M. Baccino, M. Messina, M. Musi, and L. Tessitore, Regulation of cell protein turnover and proteinase activities in relation to growth in: “Recent trends in Chemical Carcinogenesis”, P. Pani, F. Feo, and A. Columbano, eds., ESA, Cagliari (1982).Google Scholar
  6. 6.
    F. M. Baccino, L. Tessitore, and G. Bonelli, Control of protein degradation vs. growth phase in normal and neoplastic cells, Toxicol. Pathol. 12:281 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    F. M. Baccino, L. Tessitore, G. Bonelli, and C. Isidoro, Protein turnover state of tumour cells and host tissues in an experimental model, Biomed. Biochim. Acta 45:1585 (1986).PubMedGoogle Scholar
  8. 8.
    F. J. Ballard, S. E. Knowles, S. S. C. Wong, J. B. Bodner, C. M. Wood, and J. M. Gunn, Inhibition of protein breakdown in cultured cells is a consistent response to growth factors, FEBS Lett. 114:209 (1980).PubMedCrossRefGoogle Scholar
  9. 9.
    F. J. Ballard, Regulation of protein breakdown by epidermal growth factor in A431 cells, Exp. Cell Res. 157:172 (1985).PubMedCrossRefGoogle Scholar
  10. 10.
    F. J. Ballard, Regulation of intracellular protein breakdown with special reference to cultured cells, in: “Lysosomes: their Role in Protein Breakdown”, H. Glaumann and F. J. Ballard, eds., Academic Press, London (1987).Google Scholar
  11. 11.
    O. A. Scornick and V. Botbol, Protein metabolism and liver growth, in: “Lysosomes: their Role in Protein Breakdown”, H. Glaumann and F. J. Ballard, eds., Academic Press, London (1987).Google Scholar
  12. 12.
    S. M. Cockle and R. T. Dean, Derangement of regulation of protein degradation in transforming fibroblasts, Biosci. Rep. 2:107 (1982).PubMedCrossRefGoogle Scholar
  13. 13.
    T. D. Lockwood and I. A. Minassian, Protein turnover and proliferation. Failure of SV-3T3 cells to increase lysosomal proteinases, increase protein degradation and cease net protein accumulation, Biochem. J. 206:251 (1982).PubMedGoogle Scholar
  14. 14.
    P. E. Schwartze and P. O. Seglen, Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats, Exp. Cell Res. 157:15 (1985).CrossRefGoogle Scholar
  15. 15.
    A. Anastasi and R. T. Dean, Regulation of protein degradation in fibroblasts, in: “Intracellular Protein Catabolism”, E. A. Khairallah, J. S. Bond, and J. W. C. Bird, eds., Alan R. Liss, New York, (1985).Google Scholar
  16. 16.
    R. M. Gronostajski and A. B. Pardee, Protein degradation in 3T3 cells and tumorigenic transformed 3T3 cells, J. Cell. Physiol. 119:127 (1984).PubMedCrossRefGoogle Scholar
  17. 17.
    J. S. Amenta, J. Mehta and F. M. Baccino, Proteolysis associated with thymidine-induced selective cell death in L-cell cultures, this book.Google Scholar
  18. 18.
    L. Tessitore, G. Bonelli, G. Cecchini, J. S. Amenta and F. M. Baccino, Regulation of protein turnover versus growth state: ascites hepatoma as a model for study both in the animal and in vitro, Arch. Biochem. Biophys. 255:372 (1987).PubMedCrossRefGoogle Scholar
  19. 19.
    L. Tessitore, G. Bonelli, G. Cecchini, R. Autelli, J. S. Amenta and F. M. Baccino, Regulation of protein turnover vs. growth state. II. Studies on the mechanisms of initiation of acidic vacuolar proteolysis in cells of stationary ascitic hepatoma, Biochem. J. in press (1988).Google Scholar
  20. 20.
    U. Pfeifer, L. Tessitore, G. Bonelli and F. M. Baccino, Regulation of protein turnover versus growth state. III, Growth cessation is associated with activation of autophagy in Yoshida ascites hepatoma AH-130, submitted (1988).Google Scholar
  21. 21.
    J. Kovàcs, E. Fellniger, P. A. Kàrpàti, A. L. Kovàcs and L. Làzlò, The turnover of autophagic vacuoles: evaluation by quantitative electror microscopy, Biomed. Biochim. Acta 45:1543 (1986).PubMedGoogle Scholar
  22. 22.
    U. Pfeifer, Inhibition by insulin of the formation of autophagic vacuoles in rat liver, J. Cell Biol. 78:152 (1978).PubMedCrossRefGoogle Scholar
  23. 23.
    G. E. Mortimore and A. R. Poso, The lysosomal pathway of intracellular proteolysis in liver: regulation by amino acids, Adv. Enzymol. 25:257 (1986).CrossRefGoogle Scholar
  24. 24.
    P. O. Seglen and P. B. Gordon, Amino acid control of autophagic sequestration and protein degradation in isolated rat hepatocytes, J. Cell Biol. 99:435 (1984).PubMedCrossRefGoogle Scholar
  25. 25.
    J. C. Waterlow, Protein turnover with special reference to man, Quart. J. Exp. Physiol. 69:409 (1984).Google Scholar
  26. 26.
    L. Tessitore, G. Bonelli and F. M. Baccino, Early development of protein metabolic perturbations in the liver and skeletal muscle of tumour-bearing rats: a model system for cancer cachexia, Biochem. J. 241:153 (1987).PubMedGoogle Scholar
  27. 27.
    M. Olivotto, R. Caldini, M. Chevanne and M. G. Cipolleschi, The respiration-linked limiting step of tumor cell transition from the non-cycling to the cycling state: its inhibition by oxidizable substrates and its relationships to purine metabolism, J. Cell. Physiol. 116:149 (1983).PubMedCrossRefGoogle Scholar
  28. 28.
    E. O. Pettersen, N. O. Juul and O. W. Ronning, Regulation of protein metabolism of human cells during and after acute hypoxia, Cancer Res. 46:4346 (1986).PubMedGoogle Scholar
  29. 29.
    Ø. W. Rønning, T. Lindmo, E. O. Petterson and P. O. Seglen, Effect of serum step-down on protein metabolism and proliferation kinetics of NHIK 3025 cells, J. Cell. Physiol. 107:47 (1981).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Franco M. Baccino
    • 1
  • Riccardo Autelli
    • 1
  • Gabriella Bonelli
    • 1
  • Paola Costelli
    • 1
  • Ciro Isidoro
    • 1
  • Luciana Tessitore
    • 1
  1. 1.Department of Experimental Medicine and Oncology, General Pathology SectionTorino UniversityTorinoItaly

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