Advertisement

Two subclasses of EGF receptors in the human pancreatic cancer cell lines CAPAN-1 and MIA PaCa-2

  • Patricia Oustry
  • Agnès Estival
  • Lucien Pradayrol
  • Nicole Vaysse
  • François Clémente
Article
  • 21 Downloads

Summary

The existence of different classes of EGF receptors in human pancreatic cancer cells has yet not been determined. EGF binding to two cancer cell lines (CAPAN-1 and MIA PaCa-2) was studied. Two classes of EGF binding sites were characterized. The first class of EGF binding sites demonstrated a high affinity and low capacity for EGF, with aK d of 0.25±0.11 nM, close to the concentration of EGF suggested to be present in human pancreatic juice. The second class of EGF binding sites had a lower affinity and a higher capacity for EGF, with aK d of 1.78±0.61 nM. The total number of EGF binding sites was about 40,000/cell. Treatment of the cells with a phorbol ester, TPA, caused a complete loss of the high affinity binding sites and also caused a decrease in the concentration of the lower affinity binding sites present on the cells. Interestingly, with the increasing age of the cells, the concentration of both the high and low affinity EGF binding sites was significantly decreased. In the presence or absence of fetal calf serum, EGF, at concentrations higher than 1.10-10 M, exerted a dose-dependent mitogenic effect on the growth of the pancreatic cancer cells in culture. These data demonstrate the existence of two classes of binding sites for EGF on some human pancreatic cancer cells and a possible role of EGF in the growth of pancreatic tumors.

Key Words

Human pancreatic cancer EGF receptor subclasses receptor regulation proliferation protein kinase C 

References

  1. 1.
    Dembinsky A, Gregory H, Konturek SJ, Polanski M. Trophic action of Epidermal Growth Factor on the pancreas and gastro-duodenal mucosa in rats. J. Physiol. (London) 1982; 325: 35–42.Google Scholar
  2. 2.
    Puccio F, Lehy T. Oral administration of Epidermal Growth Factor in suckling rats stimulated cell DNA synthesis in fundic and antral gastric mucosae as well as in intestinal mucosa and pancreas. Regul. Peptides 1988; 20: 53–64.CrossRefGoogle Scholar
  3. 3.
    Brannon PM, Hirschi K, Korc M. Effect of Epidermal Growth Factor, Insulin and Insulin-like Growth Factor I on rat pancreatic acinar cells cultured in serum-free medium. Pancreas 1988; 3: 41–48.PubMedCrossRefGoogle Scholar
  4. 4.
    Logsdon CD, Williams J. Pancreatic acini in short term culture: regulation by EGF, carbachol, insulin and corticosterone. Am. J. Physiol. 1983; 244: G675–682.PubMedGoogle Scholar
  5. 5.
    Real FX, Rettig WJ, Chesa PG, Melamed MR, Old LJ, Mendelsohn J. Expression of Epidermal Growth Factor receptor in human cultured cells and tissues: relationship to cell lineage and stage of differentiation. Cancer Res. 1986; 46: 4726–4731.PubMedGoogle Scholar
  6. 6.
    Korc M. Epidermal Growth Factor receptor: its role in pancreatic cancer. Cancer of the exocine pancreas. Front Gastroinst. Res., vol. 12, Delmont, J.P., ed.s Karger, Basel, 1986, pp. 40–47.Google Scholar
  7. 7.
    Gamou S, Kim YS, Shimizu N. Different responses to EGF in two human carcinoma cell lines, AR431 and UCVA-1, possessing high numbers of EGF receptors. Mol. Cell. Endocrinol. 1984; 37: 205–213.PubMedCrossRefGoogle Scholar
  8. 8.
    Gill GN, Bertics PJ, Santon JB. Epidermal Growth Factor and its receptor (review). Mol. Cell. Endocrinol. 1987; 51: 169–186.PubMedCrossRefGoogle Scholar
  9. 9.
    Schlessinger J. Allosteric regulation of the Epidermal Growth Factor receptor kinase. J. Cell Biol. 1986; 103: 2067–2072.PubMedCrossRefGoogle Scholar
  10. 10.
    Ruellan C, Scemama JL, Clerc P, Fagot-Revurat P, Clemente F, Ribet A. VIP regulation of a human pancreatic cancer cell line: CAPAN-1. Peptides 1986; 7, suppl. 1: 267–271.PubMedCrossRefGoogle Scholar
  11. 11.
    Matrisian LM, Larsen BR, Finch JS, Magun BE. Further purification of Epidermal Growth Factor by high-performance liquid chromatography. Anal. Biochem. 1982; 125: 339–351.PubMedCrossRefGoogle Scholar
  12. 12.
    Munson PJ. Ligand: a computerized analysis of ligand binding data. Methods in Enzymology, vol, 92, Langone JL, Van Vunakis H, eds., Academic, New York, 1983, pp. 543–576.Google Scholar
  13. 13.
    Lowry OH, Rosebrough NJ, Far AL, Randall RJ. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 1951; 193: 265–275.PubMedGoogle Scholar
  14. 14.
    Burton K. A study of the conditions and mechanism of the diphenyl amine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochemistry 1956; 62: 315–323.Google Scholar
  15. 15.
    Korc M, Matrisian LM. Binding of Epidermal Growth Factor in rat pancreatic acini. Biochem. Biophys. Res. Commun. 1983; 111:1066–1073.PubMedCrossRefGoogle Scholar
  16. 16.
    Estival A, Mounielou P, Trocheris V, Scemama JL, Clemente F, Hollande E, Ribet A. Presence of VIP receptors in a human adenocarcinoma cell line. Modulation of the cAMP response during cell proliferation. Biochem. Biophys. Res. Commun. 1983; 111: 958–963.PubMedCrossRefGoogle Scholar
  17. 17.
    Logsdon CD, Williams JA. Epidermal growth factor binding and biological effects on mouse pancreatic acini. Gastroenterology 1983; 85: 339–345.PubMedGoogle Scholar
  18. 18.
    Korc M, Meltzer P, Trent J. Enhanced expression of epidermal growth factor receptor correlates with alterations of chromosome 7 in human pancreatic cancer. Proc. Natl. Acad. Sci. USA 1986; 83: 5141–5144.PubMedCrossRefGoogle Scholar
  19. 19.
    Hirata Y, Uchikashi M, Nakajima M, Fujita T, Matsukura S. Immunoreactive human Epidermal Growth Factor in human pancreatic juice. J. Clin. Endocr. Metab. 1982; 54: 1242–1245.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1990

Authors and Affiliations

  • Patricia Oustry
    • 1
  • Agnès Estival
    • 1
  • Lucien Pradayrol
    • 1
  • Nicole Vaysse
    • 1
  • François Clémente
    • 1
  1. 1.INSERM U.151CHU RangueilToulouseFrance

Personalised recommendations