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. 1992 Nov 15;89(22):10872–10876. doi: 10.1073/pnas.89.22.10872

Intact and amino-terminally shortened forms of insulin-like growth factor I induce mammary gland differentiation and development.

W Ruan 1, C B Newman 1, D L Kleinberg 1
PMCID: PMC50444  PMID: 1438291

Abstract

Growth hormone (GH) plays a role in regulating growth and differentiation of immature glandular structures in the mammary gland, but the mechanisms by which the hormone exerts these effects are unknown. We have previously found that GH stimulates insulin-like growth factor I (IGF-I) I mRNA production within the mammary glands of hypophysectomized rats. In this study we set out to determine if IGF-I administration could mimic the action of GH in initiating mammary gland differentiation and development. Two forms of IGF-I, intact and amino-terminally shortened [des-(1-3)-IGF-I], were found to induce the development of terminal end buds and the formation of alveolar structures in the mammary glands of hypophysectomized, castrated, and estradiol-treated sexually immature male rats. The effect of both forms of IGF-I was similar to that obtained with human GH, but the truncated form was at least 5 times more potent than intact IGF-I. These findings suggest that the inductive effect of GH on glandular differentiation is mediated by the GH-induced production of IGF-I or a related molecule within the mammary gland itself.

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Selected References

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  1. Arteaga C. L., Kitten L. J., Coronado E. B., Jacobs S., Kull F. C., Jr, Allred D. C., Osborne C. K. Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice. J Clin Invest. 1989 Nov;84(5):1418–1423. doi: 10.1172/JCI114315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Carlsson-Skwirut C., Lake M., Hartmanis M., Hall K., Sara V. R. A comparison of the biological activity of the recombinant intact and truncated insulin-like growth factor 1 (IGF-1). Biochim Biophys Acta. 1989 May 10;1011(2-3):192–197. doi: 10.1016/0167-4889(89)90209-7. [DOI] [PubMed] [Google Scholar]
  4. Clinical trial of 2-Br- -ergocryptine (CB154) in advanced breast cancer. Eur J Cancer. 1972 Apr;8(2):155–156. doi: 10.1016/0014-2964(72)90037-0. [DOI] [PubMed] [Google Scholar]
  5. Dickson R. B., Lippman M. E. Control of human breast cancer by estrogen, growth factors, and oncogenes. Cancer Treat Res. 1988;40:119–165. doi: 10.1007/978-1-4613-1733-3_6. [DOI] [PubMed] [Google Scholar]
  6. Forsyth I. A. Growth factors in mammary gland function. J Reprod Fertil. 1989 Mar;85(2):759–770. doi: 10.1530/jrf.0.0850759. [DOI] [PubMed] [Google Scholar]
  7. Francis G. L., Upton F. M., Ballard F. J., McNeil K. A., Wallace J. C. Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and biological activities compared with those of a potent truncated form. Biochem J. 1988 Apr 1;251(1):95–103. doi: 10.1042/bj2510095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Furlanetto R. W., DiCarlo J. N. Somatomedin-C receptors and growth effects in human breast cells maintained in long-term tissue culture. Cancer Res. 1984 May;44(5):2122–2128. [PubMed] [Google Scholar]
  9. Jahn G. A., Edery M., Belair L., Kelly P. A., Djiane J. Prolactin receptor gene expression in rat mammary gland and liver during pregnancy and lactation. Endocrinology. 1991 Jun;128(6):2976–2984. doi: 10.1210/endo-128-6-2976. [DOI] [PubMed] [Google Scholar]
  10. Kleinberg D. L., Niemann W., Flamm E., Cooper P., Babitsky G., Valensi Q. Primate mammary development. Effects of hypophysectomy, prolactin inhibition, and growth hormone administration. J Clin Invest. 1985 Jun;75(6):1943–1950. doi: 10.1172/JCI111910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kleinberg D. L., Ruan W., Catanese V., Newman C. B., Feldman M. Non-lactogenic effects of growth hormone on growth and insulin-like growth factor-I messenger ribonucleic acid of rat mammary gland. Endocrinology. 1990 Jun;126(6):3274–3276. doi: 10.1210/endo-126-6-3274. [DOI] [PubMed] [Google Scholar]
  12. LIPSETT M. B., PEARSON O. H. Effects of hypophysectomy in man. Med Clin North Am. 1956 May;40(3):773–786. doi: 10.1016/s0025-7125(16)34565-5. [DOI] [PubMed] [Google Scholar]
  13. LYONS W. R., LI C. H., JOHNSON R. E. The hormonal control of mammary growth and lactation. Recent Prog Horm Res. 1958;14:219–254. [PubMed] [Google Scholar]
  14. Lee K. F., DeMayo F. J., Atiee S. H., Rosen J. M. Tissue-specific expression of the rat beta-casein gene in transgenic mice. Nucleic Acids Res. 1988 Feb 11;16(3):1027–1041. doi: 10.1093/nar/16.3.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McGrath M. F., Collier R. J., Clemmons D. R., Busby W. H., Sweeny C. A., Krivi G. G. The direct in vitro effect of insulin-like growth factors (IGFs) on normal bovine mammary cell proliferation and production of IGF binding proteins. Endocrinology. 1991 Aug;129(2):671–678. doi: 10.1210/endo-129-2-671. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. NANDI S. Endocrine control of mammarygland development and function in the C3H/ He Crgl mouse. J Natl Cancer Inst. 1958 Dec;21(6):1039–1063. [PubMed] [Google Scholar]
  18. Newman C. B., Cosby H., Friesen H. G., Feldman M., Cooper P., De Crescito V., Pilon M., Kleinberg D. L. Evidence for a nonprolactin, non-growth-hormone mammary mitogen in the human pituitary gland. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8110–8114. doi: 10.1073/pnas.84.22.8110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nilsson A., Isgaard J., Lindahl A., Dahlström A., Skottner A., Isaksson O. G. Regulation by growth hormone of number of chondrocytes containing IGF-I in rat growth plate. Science. 1986 Aug 1;233(4763):571–574. doi: 10.1126/science.3523759. [DOI] [PubMed] [Google Scholar]
  20. Pearson O. H., Manni A., Arafah B. M. Antiestrogen treatment of breast cancer: an overview. Cancer Res. 1982 Aug;42(8 Suppl):3424s–3429s. [PubMed] [Google Scholar]
  21. 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]
  22. Schlechter N. L., Russell S. M., Spencer E. M., Nicoll C. S. Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7932–7934. doi: 10.1073/pnas.83.20.7932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shamay A., Cohen N., Niwa M., Gertler A. Effect of insulin-like growth factor I on deoxyribonucleic acid synthesis and galactopoiesis in bovine undifferentiated and lactating mammary tissue in vitro. Endocrinology. 1988 Aug;123(2):804–809. doi: 10.1210/endo-123-2-804. [DOI] [PubMed] [Google Scholar]
  24. Shiu R. P., Friesen H. G. Mechanism of action of prolactin in the control of mammary gland function. Annu Rev Physiol. 1980;42:83–96. doi: 10.1146/annurev.ph.42.030180.000503. [DOI] [PubMed] [Google Scholar]
  25. Silberstein G. B., Daniel C. W. Elvax 40P implants: sustained, local release of bioactive molecules influencing mammary ductal development. Dev Biol. 1982 Sep;93(1):272–278. doi: 10.1016/0012-1606(82)90259-7. [DOI] [PubMed] [Google Scholar]
  26. Yee D., Paik S., Lebovic G. S., Marcus R. R., Favoni R. E., Cullen K. J., Lippman M. E., Rosen N. Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. Mol Endocrinol. 1989 Mar;3(3):509–517. doi: 10.1210/mend-3-3-509. [DOI] [PubMed] [Google Scholar]

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