Skip to main content
SpringerLink
Log in

Gastrin releasing peptide GRP(14–27) in human breast cancer cells and in small cell lung cancer

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Immunoreactivity related to the gastrin-releasing peptide (GRP) precursor was detected in four different human breast cancer cell lines. The amounts and the characteristics in extracts from different breast carcinoma cells were compared with cell extracts from small cell lung cancer (SCLC) cells. Two different radioimmunoassays were employed, directed against the amino acid sequence 14–27 of GRP (IR-GRP) or the 42–53 amino acid sequence at the C-terminal end of the GRP precursor (GRP precursor fragment). In extracts from T47D cells cultured under serum free conditions, IR-GRP coeluted with GRP (14–27) or GRP (18–27) in Sephadex G-50 chromatography. No immunoreactivity was detected in the fractions containing high molecular weight components. In a total of 41 human breast carcinoma biopsies from different postmenopausal patients, IR-GRP was detected by immunohistological staining in 39% of the samples. When the GRP (14–27) peptide was added exogenously to breast cancer and SCLC cell lines under serumfree culture conditions, (3H)-thymidine incorporation was stimulated by GRP(14–27) in the SCLC cell lines. Of the breast cancer cell lines only the T47D cell line responded with an increase in (3H)-thymidine incorporation comparable to the increase observed with SCLC cells. Recently, it has been reported that GRP-like receptors are present in some human breast cancer cell lines, including the T47D cell line studied here. The breast cancer cell line T47D therefore expresses the GRP peptide and the receptor for GRP. The identification of GRP-like receptors on T47D cells is in accordance with our present observation of a growth response to GRP(14–27) as evaluated by increased (3H)-thymidine incorporation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Perroteau I, Salomon D, Debartoli M, Kidwell W, Hazarika P, Pardue R, Dedman J, Tam J: Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells. Breast Cancer Res Treat 7: 201–210, 1986

    Article  PubMed  Google Scholar 

  2. Bates SE, Davidson NE, Valverius EM, Feeter CE, Dickson RB, Tam JP, Kudlow JE, Lippman ME, Salomon DS: Expression of transforming growth factor and its messenger ribonucleic acid in human brast cancer: Its regulation by estrogen and its possible functional significance. Mol Endocrinol 2: 543–555, 1988

    PubMed  Google Scholar 

  3. Anastasi A, Erspamer V, Bucci M: Isolation and structure of bombesin and alytesin, two analogous active peptides from the skin of the European amphibiansBombina andAlytes. Experientia 27: 166–167, 1971

    PubMed  Google Scholar 

  4. Wood SM, Wood JR, Ghatei MA, Lee YC, O'Shaughnessy D, Bloom SA: Bombesin, somatostatin, and neurotensinlike immunoreactivity in bronchial carcinoma. J Clin Endocrinol Metab 53: 1310–1312, 1981

    PubMed  Google Scholar 

  5. Bostwick DG, Roth KA, Barchas JD, Bensch KG: Gastrin-releasing peptide immunoreactivity in intestinal carcinoids. Am J Clin Pathol 82: 428–431, 1984

    PubMed  Google Scholar 

  6. Matsubayashi S, Yanaihara C, Ohkubo M,et al. Gastrin-releasing peptide immunoreactivity in medullary thyroid carcinoma. Cancer 53: 2472–2477, 1984

    PubMed  Google Scholar 

  7. Rozengurt E, Sinnett-Smith J: Bombesin stimulation of DNA synthesis and cell division in cultures of Swiss 3T3 cells. Proc Natl Acad Sci USA 80: 2936–2940, 1983

    PubMed  Google Scholar 

  8. Willey JC, Lechner JF, Harris CC: Bombesin and the C terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal human bronchial epithelial cells. Exp Cell Res 153: 245–249, 1984

    Article  PubMed  Google Scholar 

  9. Moody TW, Carney DN, Cuttitta F, Quattrocchi K, Minna JD: High affinity receptors for bombesin/GRP-like peptides on human small cell lung cancer. Life Sci 37: 105–114, 1985

    Article  PubMed  Google Scholar 

  10. Cuttitta F, Carney DN, Mulshine J,et al. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316: 823–826, 1985

    PubMed  Google Scholar 

  11. Woll PJ, Rozengurt E: (D-Arg1, D-Phe5, D-Trp7.9, Leu11) Substance P, a potent bombesin antagonist in murine Swiss 3T3 cells, inhibits the growth of human small cell lung cancer cellsin vitro. Proc Natl Acad Sci USA 85: 1859–1863, 1988

    PubMed  Google Scholar 

  12. Walsh JH, Wong HC, Dockray GJ: Bombesin-like peptides in mammals. Fed Proc 38: 2315–2319, 1979

    PubMed  Google Scholar 

  13. Weber S, Zuckerman JE, Bostwick DG, Bensch KG, Branimir I, Raffin TA: Gastrin releasing peptide is a selective mitogen for small cell lung carcinoma cellsin vitro. J Clin Invest 75: 306–309, 1985

    PubMed  Google Scholar 

  14. Major J, Ghatei MA, Bloom SR: Bombesin-like immuno-reactivity in the pituitary gland. Experientia 39: 1158–1159, 1983

    Article  PubMed  Google Scholar 

  15. Ghatei MA, Bloom SR, Langevin H, McGregor GP, Lee YC, Adrian TE, O'Shaughnessy DJ, Blank MA, Uttenthal LO: Regional distribution of bombesin and seven other regulatory peptides in the human brain. Brain Res 293: 101–109, 1984

    Article  PubMed  Google Scholar 

  16. Tsutsumi Y, Nagura H, Watanabe K, Yanaihara N: Methods in laboratory investigation. Immunoreactivity of Nterminal fragment of gastrin-releasing peptide as a histochemical marker for pancreatobiliary duct-type cells. Lab Invest 50: 94–100, 1984

    PubMed  Google Scholar 

  17. Wharton J, Polar JM, Bloom SR, Ghatei MA, Solcia E, Brown MR, Pearse AGE: Bombesin-like immunoreactivity in the lung. Nature 273: 769–770, 1978

    PubMed  Google Scholar 

  18. Giacchetti S, Gauvillé C, Crémoux P, Bertin L, Berthon P, Abita J-P, Cuttitta F, Calvo F: Characterization in some human breast cancer cell lines, of gastrin-releasing peptide-like receptors which are absent in normal breast epithelial cells. Int J Cancer 46: 293–298, 1990

    PubMed  Google Scholar 

  19. Briand P, Lykkesfeldt AE: Loong term cultivation of a human breast cancer cell line, MCF-7, in a chemically defined medium. Effect of estradiol. Anticancer Res 6: 85–90, 1986

    PubMed  Google Scholar 

  20. Berendsen HH, de Leij L, de Vries EGE, Mesander G, Mulder NH, de Jong B, Buys CHCM, Postmus PE, Poppema S, Sluiter HJ, The HT: Characterization of three small cell lung cancer cell lines established from one patient during longitudinal follow-up. Cancer Res 48: 6891–6899, 1988

    PubMed  Google Scholar 

  21. Engelholm SA, Vindeløv L, Spang-Thomsen M, Brunner N, Tommerup N, Nielsen MH, Hansen HH: Genetic instability of cell lines derived from a single human small cell carcinoma of the lung. Eur J Cancer Clin Oncol 21: 815–824, 1985

    Article  PubMed  Google Scholar 

  22. Vangsted A, Schwartz TW: Production of gastrin releasing peptide-(18–27) and a stable fragment of its precursor in small cell lung carcinoma cells. J Clin Endocrinol Metab 70: 1586–1593, 1990

    PubMed  Google Scholar 

  23. Sheikh SP, O'Hare MMT, Tortora O, Schwartz TW: Binding of monoiodinated neuropeptide 4 to hippocampal membranes and human neuroblastoma cells. J Biol Chem 264: 6648–6654, 1989

    PubMed  Google Scholar 

  24. Lowry OH, Rosebrough NJ, Farr AL, Randall JR: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  Google Scholar 

  25. Klenow H, Flodgaard H: Both hypoxanthine and adenosine stimulate DNA synthesis independently in serumstarved L cells treated with platelet protein. Proc Natl Acad Sci USA 80: 7420–7423, 1983

    PubMed  Google Scholar 

  26. Larsen PJ, Særmark T, Mikkelsen JD: An immunohistochemical demonstration of gastrin-releasing peptide (GRP) in the rat substantia nigra. J Chem Neuroanat 2: 83–93, 1989

    PubMed  Google Scholar 

  27. Bradbury AF, Finnie MDA, Smyth DG: Mechanism of C-terminal amide formation by pituitary enzymes. Nature 298: 686–688, 1982

    Article  PubMed  Google Scholar 

  28. Reeve JR, Walsh JH, Chew P, Clark B, Hawke D, Shively JE: Amino acid sequence of three bombesin-like peptides from canine intestine extracts. J Biol Chem 258: 5582–5588, 1982

    Google Scholar 

  29. Trepel JB, Moyer JD, Cuttitta F, Frucht H, Coy DH, Natale RB, Mulshine JL, Jensen RT, Sausvill EA: A novel bombesin receptor antagonist inhibits autocrine signals in a small cell lung carcinoma cell line. Biochem Biophys Res Commun 156: 1383–1389, 1988

    Article  PubMed  Google Scholar 

  30. Gould VE, Lee I, Warren WH: Immunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung. Pathol Res Pract 183: 200–213, 1988

    PubMed  Google Scholar 

  31. Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD: Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45: 2913–2923, 1985

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. A. J. Vangsted

    Present address: Dept. of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society, Ndr. Frihavnsgade 70, DK-2100, Copenhagen, Denmark

Authors and Affiliations

  1. Dept. of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society, Ndr. Frihavnsgade 70, DK-2100, Copenhagen, Denmark

    E. V. Andersen & J. Zeuthen

  2. Department of Pathology, Roskilde Hospital, Roskilde, Denmark

    L. Nedergaard

Authors
  1. A. J. Vangsted
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. V. Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Nedergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Zeuthen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vangsted, A.J., Andersen, E.V., Nedergaard, L. et al. Gastrin releasing peptide GRP(14–27) in human breast cancer cells and in small cell lung cancer. Breast Cancer Res Tr 19, 119–128 (1991). https://doi.org/10.1007/BF01980942

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01980942

Key words

Search

Navigation