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. 1992 Aug;66(2):248–253. doi: 10.1038/bjc.1992.252

Insulin-like growth factor 1 receptors in human breast tumour: localisation and quantification by histo-autoradiographic analysis.

H Jammes 1, J P Peyrat 1, E Ban 1, M O Vilain 1, F Haour 1, J Djiane 1, J Bonneterre 1
PMCID: PMC1977795  PMID: 1323990

Abstract

To assess the precise role of IGF1 in benign and malignant breast diseases, we analysed the tissular localisation, characterised, and quantified specific insulin-like growth factor 1 (IGF1) binding sites in these heterogenous tissues, using histo-autoradiographic analysis (HAA). The 125I-IGF1 binding was performed on frozen tissue sections and analysed using 3H Ultrofilm autoradiography coupled to computerised image analysis. Competitive binding experiments using unlabelled IGF1, IGF2 and insulin showed that the tissues exhibited typical type I IGF binding sites. This specificity was confirmed by the use of alpha IR-3 monoclonal antibody, as inhibitor of 125I-IGF1 binding. IGF1 binding sites were detected in 18 human primary breast cancers, 12 benign breast tumours and two normal breast tissues. Using HAA we found that the human breast carcinomas studied exhibit a specific and high binding capacity for 125I-IGF1 exclusively localised on the proliferative epithelial component. The 125I-IGF1 binding activity of benign breast tumours or normal breast tissue was significantly lower than in cancerous tissues. There was a significant correlation between IGF1-R concentrations detected with HAA and those detected with a classical biochemical method. Moreover, HAA could be useful in further detailing whether a tumour is IGF1-R positive or negative HAA appears to be a useful method for the detection of growth factor receptors, specially in small biopsy specimens.

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Selected References

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  1. Arteaga C. L., Osborne C. K. Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. Cancer Res. 1989 Nov 15;49(22):6237–6241. [PubMed] [Google Scholar]
  2. Bohannon N. J., Figlewicz D. P., Corp E. S., Wilcox B. J., Porte D., Jr, Baskin D. G. Identification of binding sites for an insulin-like growth factor (IGF-I) in the median eminence of the rat brain by quantitative autoradiography. Endocrinology. 1986 Aug;119(2):943–945. doi: 10.1210/endo-119-2-943. [DOI] [PubMed] [Google Scholar]
  3. Bonneterre J., Peyrat J. P., Beuscart R., Demaille A. Prognostic significance of insulin-like growth factor 1 receptors in human breast cancer. Cancer Res. 1990 Nov 1;50(21):6931–6935. [PubMed] [Google Scholar]
  4. Cullen K. J., Yee D., Sly W. S., Perdue J., Hampton B., Lippman M. E., Rosen N. Insulin-like growth factor receptor expression and function in human breast cancer. Cancer Res. 1990 Jan 1;50(1):48–53. [PubMed] [Google Scholar]
  5. D'Ercole A. J., Stiles A. D., Underwood L. E. Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci U S A. 1984 Feb;81(3):935–939. doi: 10.1073/pnas.81.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Daughaday W. H., Kapadia M., Mariz I. Serum somatomedin binding proteins: physiologic significance and interference in radioligand assay. J Lab Clin Med. 1987 Mar;109(3):355–363. [PubMed] [Google Scholar]
  7. De Leon D. D., Bakker B., Wilson D. M., Hintz R. L., Rosenfeld R. G. Demonstration of insulin-like growth factor (IGF-I and -II) receptors and binding protein in human breast cancer cell lines. Biochem Biophys Res Commun. 1988 Apr 15;152(1):398–405. doi: 10.1016/s0006-291x(88)80727-7. [DOI] [PubMed] [Google Scholar]
  8. De Leon D. D., Wilson D. M., Bakker B., Lamsom G., Hintz R. L., Rosenfeld R. G. Characterization of insulin-like growth factor binding proteins from human breast cancer cells. Mol Endocrinol. 1989 Mar;3(3):567–574. doi: 10.1210/mend-3-3-567. [DOI] [PubMed] [Google Scholar]
  9. Dickson R. B., Lippman M. E. Estrogenic regulation of growth and polypeptide growth factor secretion in human breast carcinoma. Endocr Rev. 1987 Feb;8(1):29–43. doi: 10.1210/edrv-8-1-29. [DOI] [PubMed] [Google Scholar]
  10. Foekens J. A., Portengen H., van Putten W. L., Trapman A. M., Reubi J. C., Alexieva-Figusch J., Klijn J. G. Prognostic value of receptors for insulin-like growth factor 1, somatostatin, and epidermal growth factor in human breast cancer. Cancer Res. 1989 Dec 15;49(24 Pt 1):7002–7009. [PubMed] [Google Scholar]
  11. Furlanetto R. W., Underwood L. E., Van Wyk J. J., D'Ercole A. J. Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest. 1977 Sep;60(3):648–657. doi: 10.1172/JCI108816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haour F., Dussaillant M., Leblanc P., Rostène W. Mise en évidence et répartition topographique des récepteurs du LHRH chez le rat mâle normal et castré au niveau du système nerveux central. C R Acad Sci III. 1987;305(2):41–44. [PubMed] [Google Scholar]
  13. Huff K. K., Kaufman D., Gabbay K. H., Spencer E. M., Lippman M. E., Dickson R. B. Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res. 1986 Sep;46(9):4613–4619. [PubMed] [Google Scholar]
  14. Israel A., Correa F. M., Niwa M., Saavedra J. M. Quantitative determination of angiotensin II binding sites in rat brain and pituitary gland by autoradiography. Brain Res. 1984 Nov 26;322(2):341–345. doi: 10.1016/0006-8993(84)90130-6. [DOI] [PubMed] [Google Scholar]
  15. Karey K. P., Sirbasku D. A. Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17 beta-estradiol. Cancer Res. 1988 Jul 15;48(14):4083–4092. [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Lund P. K., Moats-Staats B. M., Hynes M. A., Simmons J. G., Jansen M., D'Ercole A. J., Van Wyk J. J. Somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. J Biol Chem. 1986 Nov 5;261(31):14539–14544. [PubMed] [Google Scholar]
  18. Minuto F., Del Monte P., Barreca A., Nicolin A., Giordano G. Partial characterization of somatomedin C-like immunoreactivity secreted by breast cancer cells in vitro. Mol Cell Endocrinol. 1987 Dec;54(2-3):179–184. doi: 10.1016/0303-7207(87)90155-9. [DOI] [PubMed] [Google Scholar]
  19. Monget P., Monniaux D., Durand P. Localization, characterization, and quantification of insulin-like growth factor-I-binding sites in the ewe ovary. Endocrinology. 1989 Nov;125(5):2486–2493. doi: 10.1210/endo-125-5-2486. [DOI] [PubMed] [Google Scholar]
  20. Murphy L. J., Bell G. I., Friesen H. G. Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology. 1987 Apr;120(4):1279–1282. doi: 10.1210/endo-120-4-1279. [DOI] [PubMed] [Google Scholar]
  21. Myal Y., Shiu R. P., Bhaumick B., Bala M. Receptor binding and growth-promoting activity of insulin-like growth factors in human breast cancer cells (T-47D) in culture. Cancer Res. 1984 Dec;44(12 Pt 1):5486–5490. [PubMed] [Google Scholar]
  22. Osborne C. K., Coronado E. B., Kitten L. J., Arteaga C. I., Fuqua S. A., Ramasharma K., Marshall M., Li C. H. Insulin-like growth factor-II (IGF-II): a potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor. Mol Endocrinol. 1989 Nov;3(11):1701–1709. doi: 10.1210/mend-3-11-1701. [DOI] [PubMed] [Google Scholar]
  23. Pekonen F., Partanen S., Mäkinen T., Rutanen E. M. Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer. Cancer Res. 1988 Mar 1;48(5):1343–1347. [PubMed] [Google Scholar]
  24. Peyrat J. P., Bonneterre J., Beuscart R., Djiane J., Demaille A. Insulin-like growth factor 1 receptors in human breast cancer and their relation to estradiol and progesterone receptors. Cancer Res. 1988 Nov 15;48(22):6429–6433. [PubMed] [Google Scholar]
  25. Peyrat J. P., Bonneterre J., Dusanter-Fourt I., Leroy-Martin B., Djiane J., Demaille A. Characterization of insulin-like growth factor 1 receptors (IGF1-R) in human breast cancer cell lines. Bull Cancer. 1989;76(3):311–319. [PubMed] [Google Scholar]
  26. Peyrat J. P., Bonneterre J., Laurent J. C., Louchez M. M., Amrani S., Leroy-Martin B., Vilain M. O., Delobelle A., Demaille A. Presence and characterization of insulin-like growth factor 1 receptors in human benign breast disease. Eur J Cancer Clin Oncol. 1988 Sep;24(9):1425–1431. doi: 10.1016/0277-5379(88)90332-x. [DOI] [PubMed] [Google Scholar]
  27. Pollak M. N., Perdue J. F., Margolese R. G., Baer K., Richard M. Presence of somatomedin receptors on primary human breast and colon carcinomas. Cancer Lett. 1987 Dec;38(1-2):223–230. doi: 10.1016/0304-3835(87)90218-7. [DOI] [PubMed] [Google Scholar]
  28. Pollak M. N., Polychronakos C., Yousefi S., Richard M. Characterization of insulin-like growth factor I (IGF-I) receptors of human breast cancer cells. Biochem Biophys Res Commun. 1988 Jul 15;154(1):326–331. doi: 10.1016/0006-291x(88)90688-2. [DOI] [PubMed] [Google Scholar]
  29. Rohlik Q. T., Adams D., Kull F. C., Jr, Jacobs S. An antibody to the receptor for insulin-like growth factor I inhibits the growth of MCF-7 cells in tissue culture. Biochem Biophys Res Commun. 1987 Nov 30;149(1):276–281. doi: 10.1016/0006-291x(87)91635-4. [DOI] [PubMed] [Google Scholar]
  30. Shigematsu K., Kataoka Y., Kamio T., Kurihara M., Niwa M., Tsuchiyama H. Partial characterization of insulin-like growth factor I in primary human lung cancers using immunohistochemical and receptor autoradiographic techniques. Cancer Res. 1990 Apr 15;50(8):2481–2484. [PubMed] [Google Scholar]
  31. Shigematsu K., Niwa M., Kurihara M., Yamashita K., Kawai K., Tsuchiyama H. Receptor autoradiographic localization of insulin-like growth factor-I (IGF-I) binding sites in human fetal and adult adrenal glands. Life Sci. 1989;45(5):383–389. doi: 10.1016/0024-3205(89)90624-3. [DOI] [PubMed] [Google Scholar]
  32. Talavera F., Reynolds R. K., Roberts J. A., Menon K. M. Insulin-like growth factor I receptors in normal and neoplastic human endometrium. Cancer Res. 1990 May 15;50(10):3019–3024. [PubMed] [Google Scholar]
  33. Yee D., Cullen K. J., Paik S., Perdue J. F., Hampton B., Schwartz A., Lippman M. E., Rosen N. Insulin-like growth factor II mRNA expression in human breast cancer. Cancer Res. 1988 Dec 1;48(23):6691–6696. [PubMed] [Google Scholar]
  34. Yee D., Favoni R. E., Lippman M. E., Powell D. R. Identification of insulin-like growth factor binding proteins in breast cancer cells. Breast Cancer Res Treat. 1991 Mar;18(1):3–10. doi: 10.1007/BF01975437. [DOI] [PubMed] [Google Scholar]
  35. Yee D., Favoni R. E., Lupu R., Cullen K. J., Lebovic G. S., Huff K. K., Lee P. D., Lee Y. L., Powell D. R., Dickson R. B. The insulin-like growth factor binding protein BP-25 is expressed by human breast cancer cells. Biochem Biophys Res Commun. 1989 Jan 16;158(1):38–44. doi: 10.1016/s0006-291x(89)80173-1. [DOI] [PubMed] [Google Scholar]
  36. Zapf J., Froesch E. R. Pathophysiological and clinical aspects of the insulin-like growth factors. Horm Res. 1986;24(2-3):160–165. doi: 10.1159/000180555. [DOI] [PubMed] [Google Scholar]

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