Extinction of Human Insulin-Like Growth Factor II Expression in Somatic Cell Hybrids

  • Raffaele Zarrilli
  • Vittorio Colantuoni
  • Raffaella Faraonio
  • Stefano Casola
  • Elena Rossi
  • Carmelo B. Bruni
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 293)


Insulin-like growth factor (IGF) II is a mitogenic polypeptide (1) that plays an important role in fetal and post-natal development (2). Both in human and rodents, IGF-II is a single copy gene that gives origin to a family of RNA transcripts (3-7). These heterogeneous mRNAs are originated from at least three promoters, functioning in many tissues of the rat during the embryonic and neonatal period (3,4,8). On the contrary, in adult animals, their expression is confined to the choroid plexus and to the leptomeninges (9). The human gene also utilizes three different promoters, two of them functioning in fetal liver and in most fetal tissues (5). The third one is a tissue specific promoter, active in adult liver only (6).


HepG2 Cell Somatic Cell Hybrid BRL3A2 Cell Cell Line Chromosome Hepatoma Hybrid Cell 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    E.R. Humbel, Insulin-like growth factors I and II, Eur. J. Biochem. 190:445 (1990).PubMedCrossRefGoogle Scholar
  2. 2.
    T.M DeChiara, A. Efstratiadis, and E.J. Robertson, A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting, Nature 345:78 (1990).PubMedCrossRefGoogle Scholar
  3. 3.
    R. Frunzio, L. Chiariotti, A.L. Brown, D.E. Graham, M.M. Rechler, and C.B. Bruni, Structure and expression of the rat insulin-like growth factor II (rIGF-ll) gene, J. Biol. Chem. 261:17138 (1986).PubMedGoogle Scholar
  4. 4.
    L Chiariotti, A.L. Brown, R. Frunzio, D.R. Clemmons, M.M. Rechler, and C.B. Bruni, Structure of the rat insulin-like growth factor transcriptional unit: heterogeneous transcripts are generated from two promoters by use of multiple polyadenylation sites and differential ribonucleic acid splicing, Mol. Endocrinol. 2:1115 (1988).PubMedCrossRefGoogle Scholar
  5. 5.
    P. De Pagter-Holthuizen, M. Jansen, F.M.A. van Schaik, R. van der Kammen, C. Oosterwijk, J.L. Van den Brande, and J.S. Sussenbach, The human insulin-like growth factor II gene contains two development-specific promoters, FEBS Lett. 214:259 (1987).CrossRefGoogle Scholar
  6. 6.
    P. De Pagter-Holthuizen, M. Jansen, R.A. van der Kammen, F.M.A. van Schaik, and J.S. Sussenbach, Differential expression of the human insulinlike growth factor II gene. Characterization of the IGF-II mRNA and an mRNA encoding a putative IGF-ll-associated protein, Biochim. Biophys. Acta 950:282 (1988).Google Scholar
  7. 7.
    S. Cocozza, S. Garofalo, A. Monticelli, A. Conti, L. Chiariotti, R. Frunzio, C.B. Bruni, and S. Varrone, EcoRI RFLP in the human IGF-II gene, Nucleic Acid Res. 16:2737 (1988).PubMedCrossRefGoogle Scholar
  8. 8.
    A.L. Brown, D.E. Graham, S.P. Nissley, D.J. Hill, A.J. Strain, and M.M. Rechler, Developmental regulation of insulin-like growth factor II mRNA in different rat tissues, J. Biol. Chem. 261:13144 (1986).PubMedGoogle Scholar
  9. 9.
    F. Stylianopoulou, J. Herbert, M.B. Soares, and A. Efstratiadis, Expression of the insulin-like growth factor II gene in the choroid plexus and the leptomeninges of the adult rat central nervous system, Proc. Natl. Acad. Sci. USA 85:141 (1988).PubMedCrossRefGoogle Scholar
  10. 10.
    T. Evans, T. DeChiara, and A. Efstratiadis, A promoter of the rat insulinlike growth factor II gene consists of minimal control elements, J. Mol. Biol. 199:61 (1988).PubMedCrossRefGoogle Scholar
  11. 11.
    T. Matsuguchi, K. Takahashi, K. Ikejiri, T. Ueno, H. Endo, and M. Yamamoto, Functional analysis of multiple promoters of the rat insulinlike growth factor II gene, Biochim. Biophys. Acta 1048:165 (1990).PubMedGoogle Scholar
  12. 12.
    R.L Davidson, Gene expression in somatic cell hybrids, Annu. Rev. Genet. 8:195 (1974).PubMedCrossRefGoogle Scholar
  13. 13.
    B.B. Knowles, C.C. Howe, and D.P. Aden, Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen, Science 209:497 (1980).PubMedCrossRefGoogle Scholar
  14. 14.
    C.A. Peterson, H. Gordon, Z.W. Hall, B.M. Paterson, and H. Blau, Negative control of the helix-loop-helix family of myogenic regulators in the NFB mutant, Cell 62:493 (1990).PubMedCrossRefGoogle Scholar
  15. 15.
    S.P. Nissley, P.A. Short, M.M. Rechler, J. Podskalny, and H.G. Coon, Proliferation of Buffalo rat liver cells in serum-free medium does not depend upon multiplication-stimulating activity (MSA), Cell 11:441 (1977).PubMedCrossRefGoogle Scholar
  16. 16.
    M. Mevel-Ninio, and M.C. Weiss, Immunofluorescence analysis of the time-course of extinction, reexpression, and activaction of albumin production in rat hepatoma-mouse fibroblast heterokaryons and hybrids, J. Cell Biol. 90:339 (1981).PubMedCrossRefGoogle Scholar
  17. 17.
    A.T.C.C. CRL 8304.Google Scholar
  18. 18.
    A.M. Killary, and R.E.K. Fournier, A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrids cells, Cell 38:523 (1984).PubMedCrossRefGoogle Scholar
  19. 19.
    V. Colantuoni, A. Pirozzi, C. Blance, and R. Cortese, Negative control of liver-specific gene expression: cloned human retinol-binding protein gene is repressed in HeLa cells, EMBO J. 6:631 (1987).PubMedGoogle Scholar
  20. 20.
    R. Faraonio, M. Musy, and V. Colantuoni, Extinction of retinol-binding protein gene expression in somatic cell hybrids: identification of the target sequences, Nucleic Acid Res. (In Press).Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Raffaele Zarrilli
    • 1
  • Vittorio Colantuoni
    • 2
  • Raffaella Faraonio
    • 2
  • Stefano Casola
    • 1
  • Elena Rossi
    • 1
  • Carmelo B. Bruni
    • 1
  1. 1.Dipartimento di Biologia e Patologia Cellulare e Molecolare and Centro di Endocrinologia ed Oncologia SperimentaleC.N.R.Italy
  2. 2.Dipartimento di Biochimica e Biotecnologie Mediche, II Facoltà di Medicina e ChirurgiaUniversità degli Studi di NapoliItaly

Personalised recommendations