Skip to main content
SpringerLink
Log in
Book cover

Liver Carcinogenesis pp 1–11Cite as

Molecular Pathways in Hepatocyte Proliferation

  • Conference paper

  • 76 Accesses

Part of the book series: NATO ASI Series ((ASIH,volume 88))

Abstract

In the liver, most of the hepatocyte population resides in the G0 compartment of the cell cycle and exit into the G1 phase is achieved after an insult or injury stimulus is given (Michalopoulos, 1990). It has recently been suggested that the cellular populations which play the major role in the replacement of the functional liver mass after insult or chemical injury are mature hepatocytes, the oval cells with characteristics of both bile duct cells and fetal hepatocytes, and the Ito (fat storing) cells (Evarts et al., 1987, Evarts et al., 1990, Schirmacher et al, 1992).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Athari, A. and Jungermann, K. (1989) Direct activation by prostaglandin F2a but not thromboxane A2 of glycogenolysis via an increase in inositol 1,4,5-trisphosphate in rat hepatocytes. Biochem. Biophys. Res. Commun. 163: 1235–1242.

    Article  PubMed  CAS  Google Scholar 

  • Baffy G., Yang L, Michalopoulos, G.K. and Williamson, J.R. (1992) HGF induces calcium mobilization and inositol phosphate production in rat hepatocytes. J. Cell Physiol. 153: 332–339.

    Article  PubMed  CAS  Google Scholar 

  • Bissonnette, R.P., Echeverri, F., Mahboubi, A. and Green D.R. (1992) Apoptotic cell death induced by c-myc is inhibited bcl-2. Nature 359: 552–554.

    Article  PubMed  CAS  Google Scholar 

  • Bursch, W., Oberhammer, F. and Schulte-Hermann R. (1992) Cell death by apoptosis and its protective role against disease. Tr. Pharmacol. Sci. 13: 245–251.

    Article  CAS  Google Scholar 

  • Cantley, L.C., Auger, K., Carpenter, C., Duckworth, B., Graziani, A., Kapeller, R, and Soltoff, S. (1991) Oncogenes and signal transduction. Cell 64: 281–302

    Article  PubMed  CAS  Google Scholar 

  • Cruise, J.L., Houck, K.A. and Michalopoulos, G.K. (1985) Induction of DNA synthesis in cultured rat hepatocytes through stimulation of alpha-1 adrenoreceptor by norepinephrine. Science 227: 749–751.

    Article  PubMed  CAS  Google Scholar 

  • Etienne, P.L., Baffet, G., Desvergene, B., Boisnard-Rissel, M., Glaise, D., and Guguen-Guillouzo, C. (1988) Transient expression of c-fos and constant expression of c-myc in freshly isolated and cultured normal adult rat hepatocytes. Oncogene Res. 3: 255–262.

    PubMed  CAS  Google Scholar 

  • Evan, G.I., Wyllie, A.H., Gilbert, C.S, Littlewood, T.D, Land, H, Brooks, M, Waters, CM, Penn, L.Z, and Hancoc, D.C. (1992) Induction of apoptosis in fibroblasts by c-myc protein. Cell 69: 119–128.

    Article  PubMed  CAS  Google Scholar 

  • Evarts, R.P, Nagy, P, Marsden, E, and Thorgeirsson, S.S. (1987) In situ hybridization studies on expression of albumin and a-FP during the early stage of neoplastic transformation in rat liver. Cancer Res. 47: 5469–5475.

    PubMed  CAS  Google Scholar 

  • Evarts, R.P., Nakatsukasa, H., Marsden, E.R., Hsia, C-G, Dunsford, H.A., and Thorgeirsson, S.S. (1990) Cellular and molecular changes in the early stages of chemical hepatocarcinogenesis. Cancer Res. 50: 3439–3444.

    PubMed  CAS  Google Scholar 

  • Evarts, R.P., Nakatsukasa, H., Marsden, E.R., Hu, Z., and Thorgeirsson, S.S. (1992) Expression of TGF-a in regenerating liver and during hepatic differentiation. Mol. Carcinog. 5: 25–31.

    Article  PubMed  CAS  Google Scholar 

  • Evarts, R.P., Hu, Z., Fujio, K., Marsden, E.R., and Thorgeirsson, S.S. (1993) Activation of hepatic stem cell compartment in the rat: role of TGF-α, HGF and acidic FGF in early proliferation. Cell Growth & Diff. 4: 555–561.

    CAS  Google Scholar 

  • Fabregat, L, de Juan, G, Nakamura, T., and Benito, M. (1992) Growth stimulation of rat fetal hepatocytes in response to HGF; modulation of c-myc and c-fos expression. Biochem. Biophys. Res. Commun. 189: 684–690.

    Article  PubMed  CAS  Google Scholar 

  • Fouad Janat, M. and Liau G. (1992) TGF-β1 is a powerful modulator of PDGF action in vascular smooth muscle cells. J. Cell Physiol. 150: 232–242.

    Article  Google Scholar 

  • Giordano, S., Ponzetto, C., DiRenzo, M.F., Cooper, C.S., and Comoglio, P.M. (1989) Nature 339: 155–156.

    Article  PubMed  CAS  Google Scholar 

  • Goldfarb, M. (1990) The fibroblast growth factor family. Cell Growth Differ. 1: 439–445.

    PubMed  CAS  Google Scholar 

  • Hu, Z., Evarts, R.P., Fujio, K., Marsden, E.R., and Thorgeirsson, S.S. (1993) Expression of HGF and c-met gene during hepatic differentiation and liver development in the rat. Am. J. Pathol. 142: 1823–1830.

    PubMed  CAS  Google Scholar 

  • Kost, D.P. and Michalopoulos, G.K. (1990) Effect of EGF on the expression of protooncogenes c-myc and c-Ha-ras in short-term primary hepatocyte culture. J. Cell Physiol. 144: 122–127.

    Article  PubMed  CAS  Google Scholar 

  • Kruijer, W., Skelly, H., Botteri, F., van der Putten, H., Barber, J.R., Verma, I.M., and Leffert, H.L. (1986) Protooncogene expression in regenerating liver is stimulated in cultures of primary adult rat hepatocytes. J. Biol. Chem. 7929–7933.

    Google Scholar 

  • Lindroos, P.M., Zarnegar, R. and Michalopoulos, GK. (1991) Hepatic growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration. Hepatology 13: 743–750.

    Article  PubMed  CAS  Google Scholar 

  • Liu, K-X., Kato, Y., Narukawa, M., Kim, D-G, Hanano, M., Higuchi, O., Nakamura T., and Sugiyama, Y. (1992) Importance of the liver in plasma clearance of hepatocyte growth factor in rats. Am. J. Physiol. 26: G642–G649.

    Google Scholar 

  • Marker, A.J., Galloway, E., Palmer, S., Nakamura, T., Gould, G.W., McSween, R.N.M., and Bushfield, M. (1992) Role of the adenylate cyclase, phosphoinositidase C and receptor tyrosyl kinase systems in the control of hepatocyte proliferation by hepatocyte growth factor. Biochem. Pharmacol. 44: 1037–1043.

    Article  PubMed  CAS  Google Scholar 

  • Marsden, E.R., Hu, Z., Fujio, K., Nakatsukasa, H., Thorgeirsson, S.S. and Evarts, R.P. (1992) Expression of acidic FGF in regenerating liver and during hepatic differentiation. Lab. Invest. 67: 427–433.

    PubMed  CAS  Google Scholar 

  • Matsumoto, K., Tajima, H., Hamanoue, M., Kohno, S., Kinoshita, T., and Nakamura, T. (1992) Identification and characterization of “injurin” an inducer of expression of the gene for hepatocyte growth factor. Proc. Natl. Acad. Sci. U.S.A. 89: 3800–3804.

    Article  PubMed  CAS  Google Scholar 

  • Mead, J.E. and Fausto, N. (1989) TGF-a may be a physiological regulator of liver regeneration by means of an autocrine mechanism. Proc. Natl. Acad. Sci. U.S.A. 86: 1558–1562.

    Article  PubMed  CAS  Google Scholar 

  • Melien, O., Wisnes, R., Refsnes, M., Gladhaug, LP., and Christoffersen, T. (1988) Pertussis toxin abolishes the inhibitory effect of prostaglandins E1,E2,I2 and F2a on hormone-induced cAMP accumulation in cultured hepatocytes. Eur. J. Biochem. 172: 293–297.

    Article  PubMed  CAS  Google Scholar 

  • Meyer, D.J., Yancy, M. and Revel, J.-P. (1981) Intercellular communication in normal and regenerating rat liver: a quantitative analysis. J. Cell Biol. 91: 505–523.

    Article  PubMed  CAS  Google Scholar 

  • Michalopoulos, G.K. (1990) Liver regeneration: Molecular mechanisms of growth control. FASEB J. 4: 240–249.

    Google Scholar 

  • Michalopoulos, G.K. and Zarnegar, R. (1992) Hepatocyte Growth Factor. Hepatology 15: 149–155.

    Article  PubMed  CAS  Google Scholar 

  • Mine, T., Kojima, I. and Ogata E. (1990) Mechanisms of prostaglandin E2-induced glucose production in rat hepatocytes. Endocrinol. 126: 2831–2836.

    Article  CAS  Google Scholar 

  • Montesano, R., Vassali, J-D., Baird, A., Guillemin, R., and Orci, L. (1986) Basic FGF induces angiogenesis in vitro. Proc. Natl. Acad. Sci. U.S.A. 83: 7297–7301.

    Article  PubMed  CAS  Google Scholar 

  • Nakamura, T., Tomomura, A., Noda, C., Shimoji, M., and Ichihara, A. (1983)

    Google Scholar 

  • Acquisition of a β-adrenergic response by adult rat hepatocytes during primary culture. J. Biol. Chem. 258: 9283–9289.

    Google Scholar 

  • Nakamura, T., Nakayama, Y. and Ichihara, A. (1984) Reciprocal modulation of growth and liver functions of mature rat hepatocytes in primary culture by an extract of hepatic plasma membranes. J. Biol. Chem. 259: 8056–8058.

    PubMed  CAS  Google Scholar 

  • Nakamura, T., Teramoto, H. and Ichihara, A. (1986) Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc. Natl. Acad. Sci. U.S.A. 83: 6489–6493.

    Article  PubMed  CAS  Google Scholar 

  • Nakatsukasa, H., Evarts, R.P., Hsia, C-G, and Thorgeirsson, S.S. (1990) TGF-β1 and type I procollagen transcripts during regeneration and early fibrosis of rat liver. Lab. Invest. 63: 171–180.

    PubMed  CAS  Google Scholar 

  • Naldini, L., Vigna, E., Narshiman, R.P., Gaudino, G, Zarnegar, R., Michalopoulos, G.K., and Comoglio, P.M. (1991) HGF stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-met. Oncogene 6: 501–504.

    PubMed  CAS  Google Scholar 

  • Oberhammer, F., Bursch, W., Parzefall, W., Breit, P., Erber, E., Stadler, M., and Schulte-Hermann, R. (1991) Effect of TGF-β on cell death of cultured rat hepatocytes. Cancer Res. 51: 2478–2485.

    PubMed  CAS  Google Scholar 

  • Okano, Y., Mizuno, K., Nakamura, T., and Nozawa, Y. (1993) Tyrosine phosphorylation of PLGγ in c-met/HGF receptor-stimulated hepatocytes: comparison with HepG2 hepatocarcinoma cells. Biochem. Biophys. Res. Commun. 190: 842–848.

    Article  PubMed  CAS  Google Scholar 

  • Ramadori, G, Neubauer, K., Odenthal, M., Nakamura, T., Knittel, T., Schwogler, K.-H., and Meyer zum Buschenfelde (1992) The gene of HGF is expressed in fat-storing cells of rat liver and is downregulated during cell growth and by TGF-γ. Biochem. Biophys. Res. Commun. 183: 739–742.

    Article  PubMed  CAS  Google Scholar 

  • Refsnes, M., Thoresen, G.H., Sandnes, D., Dajani, O.F., Dajani, L., and Christoffersen, T. (1992) Stimulatory and inhibitory effects of catecholamines on DNA synthesis in primary rat hepatocyte cultures: Role of alpha1- and beta-adrenergic mechanisms. J. Cell Physiol. 151: 164–171.

    Article  PubMed  CAS  Google Scholar 

  • Schrimacher, P., Geerts, A., Pietrangelo, A., Dienes, H.P., and Rogler, C.E. (1992) HGF/hepatopoietin A is expressed in fat storing cells from rat liver but not myofibroblast-like cells derived from fat-storing cells. Hepatology 15: 5–11.

    Article  Google Scholar 

  • Skouteris, G.G., Ord, M.G and Stocken, L.A. (1988) Regulation of the proliferation of primary rat hepatocytes by eicosanoids. J. Cell Physiol. 135: 516–520.

    Article  PubMed  CAS  Google Scholar 

  • Skouteris, G.G. and Kaser M.R. (1991) Prostaglandins E2 and F2a mediate the increase in c-myc expression induced by EGF in primary rat hepatocyte cultures. Biochem. Biophys. Res. Commun. 178: 1240–1246.

    Article  PubMed  CAS  Google Scholar 

  • Skouteris, G.G. and McMenamin, M. (1992) TGF-a-induced DNA synthesis and c-myc expression in primary rat hepatocyte cultures is modulated by indomethacin. Biochem. J. 281: 729–733.

    PubMed  CAS  Google Scholar 

  • Skouteris, G.G. and Kaser M.R. (1992) Expression of exogenous c-myc oncogene does not initiate DNA synthesis in primary rat hepatocyte cultures. J. Cell Physiol. 150: 353–359.

    Article  PubMed  CAS  Google Scholar 

  • Strain, A.J., Ismail, T., Tsubouchi, H., Arakaki, N., Hishida, T., Kitamura, N., Daikuhara, Y., and McMaster, P. (1991) Native and recombinant hHGF are highly potent promoters of DNA synthesis in both human and rat hepatocytes. J. Clin. Invest. 87: 1853–1857.

    Article  PubMed  CAS  Google Scholar 

  • Stromblad, S. and Andersson, G. (1993) The coupling between TGF-α and the EGF receptor during rat liver regeneration. Exp. Cell Res. 204: 321–328.

    Article  PubMed  CAS  Google Scholar 

  • Thoresen, G.H., Sand, T.E., Refsnes, M., Dajani, O.F., Curen, T.K., Gladhaug, I.P., Killi, A., and Christoffersen, T. (1990) Dual effects of glucagon and cAMP on DNA synthesis in cultured rat hepatocytes: Stimulatory regulation in early Gl and inhibition shortly before the S phase entry. J. Cell Physiol. 144: 371–382.

    Article  Google Scholar 

  • Traub, O., Druge, P.M. and Willecke, K. (1983) Degradation and resynthesis of gap junction protein in plasma membranes of regenerating liver after partial hepatectomy or cholestasis. Proc. Natl. Acad. Sci. U.S.A. 80: 755–759.

    Article  PubMed  CAS  Google Scholar 

  • Yee, A.G. and Revel, J.-P. (1978) Loss and reappearance of gap junctions in regenerating liver. J. Cell Biol. 78: 554–564.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Applied Tumor Virology, Laboratory of Virus-Host Cell interactions, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120, Heidelberg, Germany

    George G. Skouteris

Authors
  1. George G. Skouteris
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Applied Tumor Virology, Laboratory of Virus-Host Cell Interactions, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120, Heidelberg, Germany

    George G. Skouteris

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Skouteris, G.G. (1994). Molecular Pathways in Hepatocyte Proliferation. In: Skouteris, G.G. (eds) Liver Carcinogenesis. NATO ASI Series, vol 88. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79215-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-79215-1_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79217-5

  • Online ISBN: 978-3-642-79215-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation