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The Role of Endocrine Insulin-Like Growth Factor-I and Insulin in Breast Cancer

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Abstract

Epidemiologic studies demonstrate that breast cancer is the most common type of cancer diagnosed in women and is a significant cause of morbidity and mortality. While there are many risk factors known to be associated with increased breast cancer risk, this review will focus specifically on circulating IGF-I, hyperinsulinemia, and type 2 diabetes. Their effects on promoting breast cancer development, progression, and adverse outcomes have been demonstrated in both animal and human studies, suggesting that the IGF system is a potential target for breast cancer therapy. In addition, in the clinical setting, emphasizing metabolic risk modifications to patients including weight loss, dietary changes, and diabetes control may also play an important role in breast cancer risk reduction.

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Abbreviations

IGF:

insulin-like growth factor

IGFBP:

insulin-like growth factor binding protein

BMI:

body mass index

IGF-IR:

insulin-like growth factor-I receptor

IR:

insulin receptor

IRS:

insulin receptor substrate

PI3K:

phosphatidylinositol 3-kinase

MAPK:

mitogen-activated protein kinase

ER:

estrogen receptor

TEB:

terminal end bud

GH:

growth hormone

GHRH:

growth hormone releasing hormone

JAK:

janus kinase

STAT:

signal transducer and activator of transcription

ALS:

acid labile subunit

MMTV:

mouse mammary tumor virus

SDR:

spontaneous dwarf rat

LID:

Liver IGF-I Deficient

DMBA:

7,12-dimethylbenz(a)anthracene

SV40-LTA:

SV40 large T antigen

SHBG:

sex hormone binding globulin

MCK:

muscle creatine kinase

PyVmT:

polyoma virus middle T antigen

References

  1. Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer. 2004;4(7):505–18. doi:10.1038/nrc1387.

    Article  PubMed  CAS  Google Scholar 

  2. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B. Diabetes mellitus and breast cancer. Lancet Oncol. 2005;6(2):103–11. doi:10.1016/S1470-2045(05)01736-5.

    Article  PubMed  CAS  Google Scholar 

  3. American Cancer Society. Facts and figures 2005. Atlanta: American Cancer Society; 2005.

    Google Scholar 

  4. Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001;2(3):133–40. doi:10.1016/S1470-2045(00)00254-0.

    Article  PubMed  CAS  Google Scholar 

  5. Juul A, Dalgaard P, Blum WF, Bang P, Hall K, Michaelsen KF, et al. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab. 1995;80(8):2534–42. doi:10.1210/jc.80.8.2534.

    Article  PubMed  CAS  Google Scholar 

  6. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418):1346–53. doi:10.1016/S0140-6736(04)16044-3.

    Article  PubMed  CAS  Google Scholar 

  7. Shi R, Yu H, McLarty J, Glass J. IGF-I and breast cancer: a meta-analysis. Int J Cancer. 2004;111(3):418–23. doi:10.1002/ijc.20233.

    Article  PubMed  CAS  Google Scholar 

  8. Fletcher O, Gibson L, Johnson N, Altmann DR, Holly JM, Ashworth A, et al. Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review. Cancer Epidemiol Biomark Prev. 2005;14(1):2–19.

    CAS  Google Scholar 

  9. Schernhammer ES, Holly JM, Pollak MN, Hankinson SE. Circulating levels of insulin-like growth factors, their binding proteins, and breast cancer risk. Cancer Epidemiol Biomark Prev. 2005;14(3):699–704. doi:10.1158/1055-9965.EPI-04-0561.

    Article  CAS  Google Scholar 

  10. Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998;351(9113):1393–6. doi:10.1016/S0140-6736(97)10384-1.

    Article  PubMed  CAS  Google Scholar 

  11. Rinaldi S, Peeters PH, Berrino F, Dossus L, Biessy C, Olsen A, et al. IGF-I, IGFBP-3 and breast cancer risk in women: the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer. 2006;13(2):593–605. doi:10.1677/erc.1.01150.

    Article  PubMed  CAS  Google Scholar 

  12. Schernhammer ES, Holly JM, Hunter DJ, Pollak MN, Hankinson SE. Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II. Endocr Relat Cancer. 2006;13(2):583–92. doi:10.1677/erc.1.01149.

    Article  PubMed  CAS  Google Scholar 

  13. Al-Zahrani A, Sandhu MS, Luben RN, Thompson D, Baynes C, Pooley KA, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet. 2006;15(1):1–10. doi:10.1093/hmg/ddi398.

    Article  PubMed  CAS  Google Scholar 

  14. Renehan AG, Harvie M, Howell A. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on. Endocr Relat Cancer. 2006;13(2):273–8. doi:10.1677/erc.1.01219.

    Article  PubMed  CAS  Google Scholar 

  15. Cleary MP, Maihle NJ. The role of body mass index in the relative risk of developing premenopausal versus postmenopausal breast cancer. Proc Soc Exp Biol Med. 1997;216(1):28–43.

    PubMed  CAS  Google Scholar 

  16. Stephenson GD, Rose DP. Breast cancer and obesity: an update. Nutr Cancer. 2003;45(1):1–16. doi:10.1207/S15327914NC4501_1.

    Article  PubMed  CAS  Google Scholar 

  17. Newman SC, Lees AW, Jenkins HJ. The effect of body mass index and oestrogen receptor level on survival of breast cancer patients. Int J Epidemiol. 1997;26(3):484–90. doi:10.1093/ije/26.3.484.

    Article  PubMed  CAS  Google Scholar 

  18. Yancik R, Wesley MN, Ries LA, Havlik RJ, Edwards BK, Yates JW. Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA. 2001;285(7):885–92. doi:10.1001/jama.285.7.885.

    Article  PubMed  CAS  Google Scholar 

  19. Satariano WA, Ragland DR. The effect of comorbidity on 3-year survival of women with primary breast cancer. Ann Intern Med. 1994;120(2):104–10.

    PubMed  CAS  Google Scholar 

  20. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE. Diabetes mellitus and breast cancer: a retrospective population-based cohort study. Breast Cancer Res Treat. 2006;98(3):349–56. doi:10.1007/s10549-006-9172-5.

    Article  PubMed  Google Scholar 

  21. Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schunemann HJ, et al. Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomark Prev. 2002;11(11):1361–8.

    CAS  Google Scholar 

  22. Del Giudice ME, Fantus IG, Ezzat S, McKeown-Eyssen G, Page D, Goodwin PJ. Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat. 1998;47(2):111–20. doi:10.1023/A:1005831013718.

    Article  PubMed  CAS  Google Scholar 

  23. Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20(1):42–51. doi:10.1200/JCO.20.1.42.

    Article  PubMed  CAS  Google Scholar 

  24. Hjalgrim H, Frisch M, Ekbom A, Kyvik KO, Melbye M, Green A. Cancer and diabetes—a follow-up study of two population-based cohorts of diabetic patients. J Intern Med. 1997;241(6):471–5.

    PubMed  CAS  Google Scholar 

  25. De Meyts P, Whittaker J. Structural biology of insulin and IGF1 receptors: implications for drug design. Nat Rev Drug Discov. 2002;1(10):769–83. doi:10.1038/nrd917.

    Article  PubMed  CAS  Google Scholar 

  26. Belfiore A. The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. Curr Pharm Des. 2007;13(7):671–86. doi:10.2174/138161207780249173.

    Article  PubMed  CAS  Google Scholar 

  27. Moller DE, Yokota A, Caro JF, Flier JS. Tissue-specific expression of two alternatively spliced insulin receptor mRNAs in man. Mol Endocrinol. 1989;3(8):1263–9.

    PubMed  CAS  Google Scholar 

  28. Mosthaf L, Grako K, Dull TJ, Coussens L, Ullrich A, McClain DA. Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO J. 1990;9(8):2409–13.

    PubMed  CAS  Google Scholar 

  29. Pandini G, Frasca F, Mineo R, Sciacca L, Vigneri R, Belfiore A. Insulin/insulin-like growth factor I hybrid receptors have different biological characteristics depending on the insulin receptor isoform involved. J Biol Chem. 2002;277(42):39684–95. doi:10.1074/jbc.M202766200.

    Article  PubMed  CAS  Google Scholar 

  30. Papa V, Belfiore A. Insulin receptors in breast cancer: biological and clinical role. J Endocrinol Investig. 1996;19(5):324–33.

    CAS  Google Scholar 

  31. Blakesley VA, Stannard BS, Kalebic T, Helman LJ, LeRoith D. Role of the IGF-I receptor in mutagenesis and tumor promotion. J Endocrinol. 1997;152(3):339–44. doi:10.1677/joe.0.1520339.

    Article  PubMed  CAS  Google Scholar 

  32. Papa V, Gliozzo B, Clark GM, McGuire WL, Moore D, Fujita-Yamaguchi Y, et al. Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer. Cancer Res. 1993;53(16):3736–40.

    PubMed  CAS  Google Scholar 

  33. Shimizu C, Hasegawa T, Tani Y, Takahashi F, Takeuchi M, Watanabe T, et al. Expression of insulin-like growth factor 1 receptor in primary breast cancer: immunohistochemical analysis. Human Pathol. 2004;35(12):1537–42. doi:10.1016/j.humpath.2004.09.005.

    Article  CAS  Google Scholar 

  34. Railo MJ, von Smitten K, Pekonen F. The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients. Eur J Cancer. 1994;30A(3):307–11. doi:10.1016/0959-8049(94)90247-X.

    Article  PubMed  CAS  Google Scholar 

  35. Ueda S, Tsuda H, Sato K, Takeuchi H, Shigekawa T, Matsubara O, et al. Alternative tyrosine phosphorylation of signaling kinases according to hormone receptor status in breast cancer overexpressing the insulin-like growth factor receptor type 1. Cancer Sci. 2006;97(7):597–604. doi:10.1111/j.1349-7006.2006.00228.x.

    Article  PubMed  CAS  Google Scholar 

  36. Papa V, Pezzino V, Costantino A, Belfiore A, Giuffrida D, Frittitta L, et al. Elevated insulin receptor content in human breast cancer. J Clin Invest. 1990;86(5):1503–10. doi:10.1172/JCI114868.

    Article  PubMed  CAS  Google Scholar 

  37. Mathieu MC, Clark GM, Allred DC, Goldfine ID, Vigneri R. Insulin receptor expression and clinical outcome in node-negative breast cancer. Proc Assoc Am Physicians. 1997;109(6):565–71.

    PubMed  CAS  Google Scholar 

  38. Sciacca L, Costantino A, Pandini G, Mineo R, Frasca F, Scalia P, et al. Insulin receptor activation by IGF-II in breast cancers: evidence for a new autocrine/paracrine mechanism. Oncogene. 1999;18(15):2471–9. doi:10.1038/sj.onc.1202600.

    Article  PubMed  CAS  Google Scholar 

  39. Yamaguchi Y, Flier JS, Benecke H, Ransil BJ, Moller DE. Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology. 1993;132(3):1132–8. doi:10.1210/en.132.3.1132.

    Article  PubMed  CAS  Google Scholar 

  40. McClain DA. Different ligand affinities of the two human insulin receptor splice variants are reflected in parallel changes in sensitivity for insulin action. Mol Endocrinol. 1991;5(5):734–9.

    PubMed  CAS  Google Scholar 

  41. Kleinberg DL. Early mammary development: growth hormone and IGF-1. J Mammary Gland Biol Neoplasia. 1997;2(1):49–57. doi:10.1023/A:1026373513521.

    Article  PubMed  CAS  Google Scholar 

  42. Ruan W, Catanese V, Wieczorek R, Feldman M, Kleinberg DL. Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid. Endocrinology. 1995;136(3):1296–302. doi:10.1210/en.136.3.1296.

    Article  PubMed  CAS  Google Scholar 

  43. Ruan W, Kleinberg DL. Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development. Endocrinology. 1999;140(11):5075–81. doi:10.1210/en.140.11.5075.

    Article  PubMed  CAS  Google Scholar 

  44. Mauras N, Haymond MW. Are the metabolic effects of GH and IGF-I separable? Growth Horm IGF Res. 2005;15(1):19–27. doi:10.1016/j.ghir.2004.12.003.

    Article  PubMed  CAS  Google Scholar 

  45. Pollak MN, 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;154(1):326–31. doi:10.1016/0006-291X(88)90688-2.

    Article  PubMed  CAS  Google Scholar 

  46. Arteaga CL, Osborne CK. Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. Cancer Res. 1989;49(22):6237–41.

    PubMed  CAS  Google Scholar 

  47. Arteaga CL, Kitten LJ, Coronado EB, Jacobs S, Kull FC Jr, Allred DC, et al. Blockade of the type I somatomedin receptor inhibits growth of human breast cancer cells in athymic mice. J Clin Invest. 1989;84(5):1418–23. doi:10.1172/JCI114315.

    Article  PubMed  CAS  Google Scholar 

  48. Hadsell DL, Greenberg NM, Fligger JM, Baumrucker CR, Rosen JM. Targeted expression of des(1-3) human insulin-like growth factor I in transgenic mice influences mammary gland development and IGF-binding protein expression. Endocrinology. 1996;137(1):321–30. doi:10.1210/en.137.1.321.

    Article  PubMed  CAS  Google Scholar 

  49. Hadsell DL, Murphy KL, Bonnette SG, Reece N, Laucirica R, Rosen JM. Cooperative interaction between mutant p53 and des(1–3)IGF-I accelerates mammary tumorigenesis. Oncogene. 2000;19(7):889–98. doi:10.1038/sj.onc.1203386.

    Article  PubMed  CAS  Google Scholar 

  50. Carboni JM, Lee AV, Hadsell DL, Rowley BR, Lee FY, Bol DK, et al. Tumor development by transgenic expression of a constitutively active insulin-like growth factor I receptor. Cancer Res. 2005;65(9):3781–7. doi:10.1158/0008-5472.CAN-04-4602.

    Article  PubMed  CAS  Google Scholar 

  51. Emerman JT, Leahy M, Gout PW, Bruchovsky N. Elevated growth hormone levels in sera from breast cancer patients. Horm Metab Res. 1985;17(8):421–4.

    Article  PubMed  CAS  Google Scholar 

  52. Schwarz M, Tindall GT, Nixon DW. Transsphenoidal hypophysectomy in disseminated breast cancer. South Med J. 1981;74(3):315–7.

    PubMed  CAS  Google Scholar 

  53. Silverberg GD, Britt RH. Transsphenoidal hypophysectomy in the treatment of metastatic breast and prostate carcinoma. West J Med. 1979;130(3):191–5.

    PubMed  CAS  Google Scholar 

  54. Ray BS, Pearson OH. Hypophysectomy in treatment of disseminated breast cancer. Surg Clin North Am. 1962;42:419–33.

    PubMed  CAS  Google Scholar 

  55. Mukhina S, Mertani HC, Guo K, Lee KO, Gluckman PD, Lobie PE. Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone. Proc Natl Acad Sci U S A. 2004;101(42):15166–71. doi:10.1073/pnas.0405881101.

    Article  PubMed  CAS  Google Scholar 

  56. Tornell J, Carlsson B, Pohjanen P, Wennbo H, Rymo L, Isaksson O. High frequency of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice created from two different strains of mice. J Steroid Biochem Mol Biol. 1992;43(1–3):237–42. doi:10.1016/0960-0760(92)90213-3.

    Article  PubMed  CAS  Google Scholar 

  57. Tornell J, Rymo L, Isaksson OG. Induction of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice. Int J Cancer. 1991;49(1):114–7. doi:10.1002/ijc.2910490121.

    Article  PubMed  CAS  Google Scholar 

  58. Godfrey P, Rahal JO, Beamer WG, Copeland NG, Jenkins NA, Mayo KE. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet. 1993;4(3):227–32. doi:10.1038/ng0793-227.

    Article  PubMed  CAS  Google Scholar 

  59. Jansson JO, Downs TR, Beamer WG, Frohman LA. Receptor-associated resistance to growth hormone-releasing factor in dwarf “little” mice. Science. 1986;232(4749):511–2. doi:10.1126/science.3008329.

    Article  PubMed  CAS  Google Scholar 

  60. Yang XF, Beamer WG, Huynh H, Pollak M. Reduced growth of human breast cancer xenografts in hosts homozygous for the lit mutation. Cancer Res. 1996;56(7):1509–11.

    PubMed  CAS  Google Scholar 

  61. Takeuchi T, Suzuki H, Sakurai S, Nogami H, Okuma S, Ishikawa H. Molecular mechanism of growth hormone (GH) deficiency in the spontaneous dwarf rat: detection of abnormal splicing of GH messenger ribonucleic acid by the polymerase chain reaction. Endocrinology. 1990;126(1):31–8.

    PubMed  CAS  Google Scholar 

  62. Swanson SM, Unterman TG. The growth hormone-deficient Spontaneous Dwarf rat is resistant to chemically induced mammary carcinogenesis. Carcinogenesis. 2002;23(6):977–82. doi:10.1093/carcin/23.6.977.

    Article  PubMed  CAS  Google Scholar 

  63. Thordarson G, Semaan S, Low C, Ochoa D, Leong H, Rajkumar L, et al. Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments. Breast Cancer Res Treat. 2004;87(3):277–90. doi:10.1007/s10549-004-9504-2.

    Article  PubMed  CAS  Google Scholar 

  64. Li S, Crenshaw EB 3rd, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature. 1990;347(6293):528–33. doi:10.1038/347528a0.

    Article  PubMed  CAS  Google Scholar 

  65. Bielschowsky F, Bielschowsky M. Carcinogenesis in the pituitary dwarf mouse. The response to methylcholanthrene injected subcutaneously. Br J Cancer. 1959;13:302–5.

    PubMed  CAS  Google Scholar 

  66. Alderman JM, Flurkey K, Brooks NL, Naik SB, Gutierrez JM, Srinivas U, et al. Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice. Exp Gerontol 2008, in press.

  67. Gil-Puig C, Seoane S, Blanco M, Macia M, Garcia-Caballero T, Segura C, et al. Pit-1 is expressed in normal and tumorous human breast and regulates GH secretion and cell proliferation. Eur J Endocrinol. 2005;153(2):335–44. doi:10.1530/eje.1.01962.

    Article  PubMed  CAS  Google Scholar 

  68. Ikeno Y, Bronson RT, Hubbard GB, Lee S, Bartke A. Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci. 2003;58(4):291–6.

    PubMed  Google Scholar 

  69. Yakar S, Liu JL, Stannard B, Butler A, Accili D, Sauer B, et al. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci U S A. 1999;96(13):7324–9. doi:10.1073/pnas.96.13.7324.

    Article  PubMed  CAS  Google Scholar 

  70. Wu Y, Cui K, Miyoshi K, Hennighausen L, Green JE, Setser J, et al. Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. Cancer Res. 2003;63(15):4384–8.

    PubMed  CAS  Google Scholar 

  71. Nunez NP, Perkins SN, Smith NC, Berrigan D, Berendes DM, Varticovski L, et al. Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones. Nutr Cancer. 2008;60(4):534–41. doi:10.1080/01635580801966195.

    Article  PubMed  CAS  Google Scholar 

  72. Hakkak R, Holley AW, Macleod SL, Simpson PM, Fuchs GJ, Jo CH, et al. Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats. Breast Cancer Res. 2005;7(5):R627–33. doi:10.1186/bcr1263.

    Article  PubMed  CAS  Google Scholar 

  73. Rose DP, Haffner SM, Baillargeon J. Adiposity, the metabolic syndrome, and breast cancer in African-American and white American women. Endocr Rev. 2007;28(7):763–77. doi:10.1210/er.2006-0019.

    Article  PubMed  CAS  Google Scholar 

  74. Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol. 2004;159(12):1160–7. doi:10.1093/aje/kwh161.

    Article  PubMed  Google Scholar 

  75. Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE. Increased prevalence of prior breast cancer in women with newly diagnosed diabetes. Breast Cancer Res Treat. 2006;98(3):303–9. doi:10.1007/s10549-006-9166-3.

    Article  PubMed  Google Scholar 

  76. Panno ML, Salerno M, Pezzi V, Sisci D, Maggiolini M, Mauro L, et al. Effect of oestradiol and insulin on the proliferative pattern and on oestrogen and progesterone receptor contents in MCF-7 cells. J Cancer Res Clin Oncol. 1996;122(12):745–9. doi:10.1007/BF01209122.

    Article  PubMed  CAS  Google Scholar 

  77. McTernan PG, Anwar A, Eggo MC, Barnett AH, Stewart PM, Kumar S. Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue. Int J Obes. 2000;24(7):875–81. doi:10.1038/sj.ijo.0801254.

    Article  CAS  Google Scholar 

  78. Plymate SR, Matej LA, Jones RE, Friedl KE. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab. 1988;67(3):460–4.

    Article  PubMed  CAS  Google Scholar 

  79. Baxter RC. Insulin-like growth factor binding proteins as glucoregulators. Metabolism. 1995;44(10 Suppl 4):12–7. doi:10.1016/0026-0495(95)90215-5.

    Article  PubMed  CAS  Google Scholar 

  80. Brismar K, Fernqvist-Forbes E, Wahren J, Hall K. Effect of insulin on the hepatic production of insulin-like growth factor-binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes. J Clin Endocrinol Metab. 1994;79(3):872–8. doi:10.1210/jc.79.3.872.

    Article  PubMed  CAS  Google Scholar 

  81. Lee PD, Giudice LC, Conover CA, Powell DR. Insulin-like growth factor binding protein-1: recent findings and new directions. Proc Soc Exp Biol Med. 1997;216(3):319–57.

    PubMed  CAS  Google Scholar 

  82. Frystyk J, Vestbo E, Skjaerbaek C, Mogensen CE, Orskov H. Free insulin-like growth factors in human obesity. Metabolism. 1995;44(10 Suppl 4):37–44. doi:10.1016/0026-0495(95)90219-8.

    Article  PubMed  CAS  Google Scholar 

  83. Nam SY, Lee EJ, Kim KR, Cha BS, Song YD, Lim SK, et al. Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Int J Obes Relat Metab Disord. 1997;21(5):355–9. doi:10.1038/sj.ijo.0800412.

    Article  PubMed  CAS  Google Scholar 

  84. Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309–14. doi:10.1126/science.123.3191.309.

    Article  PubMed  CAS  Google Scholar 

  85. Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, et al. Life without white fat: a transgenic mouse. Genes Dev. 1998;12(20):3168–81. doi:10.1101/gad.12.20.3168.

    Article  PubMed  CAS  Google Scholar 

  86. Nunez NP, Oh WJ, Rozenberg J, Perella C, Anver M, Barrett JC, et al. Accelerated tumor formation in a fatless mouse with type 2 diabetes and inflammation. Cancer Res. 2006;66(10):5469–76. doi:10.1158/0008-5472.CAN-05-4102.

    Article  PubMed  CAS  Google Scholar 

  87. Novosyadlyy RLD, Rowzee A, Lazzarino D, Pennisi PA, Kurshan N, Mejia W, et al. Type 2 diabetes accelerates normal mammary gland development and breast cancer progression. Abstract #1326-P. American Diabetes Association Scientific Sessions. June 2008.

  88. Fernandez AM, Kim JK, Yakar S, Dupont J, Hernandez-Sanchez C, Castle AL, et al. Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. Genes Dev. 2001;15(15):1926–34. doi:10.1101/gad.908001.

    Article  PubMed  CAS  Google Scholar 

  89. Sachdev D, Yee D. Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Ther. 2007;6(1):1–12. doi:10.1158/1535-7163.MCT-06-0080.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Derek LeRoith.

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Dr. Derek LeRoith is presently a consultant and speaker and receives as honorarium from Merck, Sanofi-Aventis, Pfizer, Takeda, and Novo Nordisk.

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Lann, D., LeRoith, D. The Role of Endocrine Insulin-Like Growth Factor-I and Insulin in Breast Cancer. J Mammary Gland Biol Neoplasia 13, 371–379 (2008). https://doi.org/10.1007/s10911-008-9100-x

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