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British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jan;69(1):120–124. doi: 10.1038/bjc.1994.19

Analysis of the IGF-II receptor gene copy number in breast carcinoma.

E Hébert 1, C Herbelin 1, P Bougnoux 1
PMCID: PMC1968763  PMID: 8286193

Abstract

Insulin and the insulin-like growth factors (IGFs) may be important regulators of breast cancer growth. The IGF-II receptor is identical to the mannose 6-phosphate (Man-6-P) receptor, which is involved in lysosomal enzyme pathways. In order to determine whether the Man-6-P/IGF-II receptor gene copy number is altered in breast cancer we analysed specimens of invasive breast carcinoma from 51 patients by Southern blotting. No amplification of the receptor gene was observed whatever the clinical presentation of the tumour and irrespective of a concomitant amplification of c-erbB2 or int-2 genes in several tumours. As indicated by Northern blotting, the gene is transcribed in breast tumour tissues and non-tumour breast tissue. These results suggest that the receptor gene is stable in breast carcinoma and that, if anything, the receptor involvement in breast cancer progression may be the result of a disregulation of its expression at a post-transcriptional or post-translational level.

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Selected References

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  1. Berns E. M., Klijn J. G., van Staveren I. L., Portengen H., Foekens J. A. Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. Cancer Res. 1992 Feb 15;52(4):1036–1039. [PubMed] [Google Scholar]
  2. Borg A., Sigurdsson H., Clark G. M., Fernö M., Fuqua S. A., Olsson H., Killander D., McGurie W. L. Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis. Br J Cancer. 1991 Jan;63(1):136–142. doi: 10.1038/bjc.1991.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bougnoux P., Chajes V., Lanson M., Hacene K., Body G., Couet C., Le Floch O. Prognostic significance of tumor phosphatidylcholine stearic acid level in breast carcinoma. Breast Cancer Res Treat. 1992 Mar;20(3):185–194. doi: 10.1007/BF01834624. [DOI] [PubMed] [Google Scholar]
  4. Casey G., Smith R., McGillivray D., Peters G., Dickson C. Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene. Mol Cell Biol. 1986 Feb;6(2):502–510. doi: 10.1128/mcb.6.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Cullen K. J., Smith H. S., Hill S., Rosen N., Lippman M. E. Growth factor messenger RNA expression by human breast fibroblasts from benign and malignant lesions. Cancer Res. 1991 Sep 15;51(18):4978–4985. [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  10. Figueroa J. A., Yee D. The insulin-like growth factor binding proteins (IGFBPs) in human breast cancer. Breast Cancer Res Treat. 1992;22(1):81–90. doi: 10.1007/BF01833336. [DOI] [PubMed] [Google Scholar]
  11. Gray K. M., White J. W., Costanzi C., Gillespie D., Schroeder W. T., Calabretta B., Saunders G. F. Recent amplification of an alpha satellite DNA in humans. Nucleic Acids Res. 1985 Jan 25;13(2):521–535. doi: 10.1093/nar/13.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Humbel R. E. Insulin-like growth factors I and II. Eur J Biochem. 1990 Jul 5;190(3):445–462. doi: 10.1111/j.1432-1033.1990.tb15595.x. [DOI] [PubMed] [Google Scholar]
  13. Kornfeld S. Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu Rev Biochem. 1992;61:307–330. doi: 10.1146/annurev.bi.61.070192.001515. [DOI] [PubMed] [Google Scholar]
  14. Krywicki R. F., Yee D. The insulin-like growth factor family of ligands, receptors, and binding proteins. Breast Cancer Res Treat. 1992;22(1):7–19. doi: 10.1007/BF01833329. [DOI] [PubMed] [Google Scholar]
  15. Lidereau R., Callahan R., Dickson C., Peters G., Escot C., Ali I. U. Amplification of the int-2 gene in primary human breast tumors. Oncogene Res. 1988 Feb;2(3):285–291. [PubMed] [Google Scholar]
  16. Mahmoudi M., Lin V. K. Comparison of two different hybridization systems in northern transfer analysis. Biotechniques. 1989 Apr;7(4):331-2, 334. [PubMed] [Google Scholar]
  17. Manni A., Wei L., Badger B., Zaenglein A., Leighton J., Shimasaki S., Ling N. Expression of messenger RNA for insulin-like growth factors and insulin-like growth factor binding proteins by experimental breast cancer and normal breast tissue in vivo. Endocrinology. 1992 Mar;130(3):1744–1746. doi: 10.1210/endo.130.3.1371457. [DOI] [PubMed] [Google Scholar]
  18. Milazzo G., Giorgino F., Damante G., Sung C., Stampfer M. R., Vigneri R., Goldfine I. D., Belfiore A. Insulin receptor expression and function in human breast cancer cell lines. Cancer Res. 1992 Jul 15;52(14):3924–3930. [PubMed] [Google Scholar]
  19. Minty A. J., Caravatti M., Robert B., Cohen A., Daubas P., Weydert A., Gros F., Buckingham M. E. Mouse actin messenger RNAs. Construction and characterization of a recombinant plasmid molecule containing a complementary DNA transcript of mouse alpha-actin mRNA. J Biol Chem. 1981 Jan 25;256(2):1008–1014. [PubMed] [Google Scholar]
  20. Morgan D. O., Edman J. C., Standring D. N., Fried V. A., Smith M. C., Roth R. A., Rutter W. J. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987 Sep 24;329(6137):301–307. doi: 10.1038/329301a0. [DOI] [PubMed] [Google Scholar]
  21. Osborne C. K., Clemmons D. R., Arteaga C. L. Regulation of breast cancer growth by insulin-like growth factors. J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):805–809. doi: 10.1016/0960-0760(90)90423-i. [DOI] [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. Oshima A., Nolan C. M., Kyle J. W., Grubb J. H., Sly W. S. The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells. J Biol Chem. 1988 Feb 15;263(5):2553–2562. [PubMed] [Google Scholar]
  24. Paik S. Expression of IGF-I and IGF-II mRNA in breast tissue. Breast Cancer Res Treat. 1992;22(1):31–38. doi: 10.1007/BF01833331. [DOI] [PubMed] [Google Scholar]
  25. Peyrat J. P., Bonneterre J. Type 1 IGF receptor in human breast diseases. Breast Cancer Res Treat. 1992;22(1):59–67. doi: 10.1007/BF01833334. [DOI] [PubMed] [Google Scholar]
  26. Rochefort H., Capony F., Garcia M. Cathepsin D: a protease involved in breast cancer metastasis. Cancer Metastasis Rev. 1990 Dec;9(4):321–331. doi: 10.1007/BF00049522. [DOI] [PubMed] [Google Scholar]
  27. Rochefort H., Capony F., Garcia M., Cavaillès V., Freiss G., Chambon M., Morisset M., Vignon F. Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? J Cell Biochem. 1987 Sep;35(1):17–29. doi: 10.1002/jcb.240350103. [DOI] [PubMed] [Google Scholar]
  28. Rochefort H. Cathepsin D in breast cancer. Breast Cancer Res Treat. 1990 Jul;16(1):3–13. doi: 10.1007/BF01806570. [DOI] [PubMed] [Google Scholar]
  29. Rochefort H. Cathepsin D in breast cancer: a tissue marker associated with metastasis. Eur J Cancer. 1992;28A(11):1780–1783. doi: 10.1016/0959-8049(92)90003-k. [DOI] [PubMed] [Google Scholar]
  30. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  31. Tandon A. K., Clark G. M., Chamness G. C., Chirgwin J. M., McGuire W. L. Cathepsin D and prognosis in breast cancer. N Engl J Med. 1990 Feb 1;322(5):297–302. doi: 10.1056/NEJM199002013220504. [DOI] [PubMed] [Google Scholar]
  32. Van de Vijver M. J., Nusse R. The molecular biology of breast cancer. Biochim Biophys Acta. 1991 Apr 16;1072(1):33–50. doi: 10.1016/0304-419x(91)90005-6. [DOI] [PubMed] [Google Scholar]
  33. Vignon F., Rochefort H. Interactions of pro-cathepsin D and IGF-II on the mannose-6-phosphate/IGF-II receptor. Breast Cancer Res Treat. 1992;22(1):47–57. doi: 10.1007/BF01833333. [DOI] [PubMed] [Google Scholar]
  34. Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. doi: 10.1038/319230a0. [DOI] [PubMed] [Google Scholar]
  35. Yashiro T., Tsushima T., Murakami H., Obara T., Fujimoto Y., Shizume K., Ito K. Insulin-like growth factor-II (IGF-II)/Mannose-6-phosphate receptors are increased in primary human thyroid neoplasms. Eur J Cancer. 1991;27(6):699–703. doi: 10.1016/0277-5379(91)90169-e. [DOI] [PubMed] [Google Scholar]
  36. Yee D. Can the insulin-like growth factors regulate breast cancer growth? Breast Cancer Res Treat. 1992;22(1):3–5. doi: 10.1007/BF01833328. [DOI] [PubMed] [Google Scholar]

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