Skip to main content

Calories and Cancer: The Role of Insulin-Like Growth Factor-1

  • Chapter
  • First Online:
Insulin-like Growth Factors and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The poem “On the Nature of Things,” written around 55 bc by Titus Lucretius Carus, is considered to be the first published statement about the potential impact of the overconsumption of food on risk of chronic diseases such as cancer (Lucretius 2008). This apparent connection between excess calorie intake and cancer began to develop into a working hypothesis in the mid-to-late 1800s, following the writings of John Hughes Bennett (1849) and William Lambe (1850). The first tests of the hypothesis that a calorie restriction (CR) dietary regimen can suppress tumors in animal models were reported in 1909 by Moreschi (1909) and extended by Sweet et al. in (1913) and Peyton Rous in (1914). These investigators showed that a low-calorie diet, relative to ad libitum (AL)-fed controls, inhibited the growth of transplanted tumors in mice. Intense interest in the comparison of CR versus AL-fed animals developed in the 1930s, when McCay and Crowell showed that reduced energy intake also increased lifespan in rodents (1934). CR research was further catalyzed by Tannenbaum et al., who consistently showed that the incidence of tumors in mice decreased when food intake was reduced (1944).

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Lucretius Carus, Titus. On the Nature of Things (Translated by A.E. Stallings). Penguin Press, NY, 2008.

    Google Scholar 

  • Bennett JH. On Cancerous and Canroid Growths. Sutherland and Knox, Edinburgh, 1849.

    Google Scholar 

  • Lambe W (with notes and additions by Shew, J.) Water and Vegetable Diet in Consumption, Scrofula, Cancer, Asthma and Other Chronic Diseases. Fowlers and Wells, NY, 1850.

    Google Scholar 

  • Moreschi C (1909) Beziehungen zwischen Ernahrung und Tumorwachstum. Zeitschrift fur Immunitatsforsch 2:661–675.

    Google Scholar 

  • Sweet JE, Carson-White EP, Saxon GJ. The relation of diets and of castration to the transmissible tumors of rats and mice. J Biol Chem 1913; 15:181–91.

    Google Scholar 

  • Rous P. The influence of diet on transplanted and spontaneous mouse tumors. J Exp Med 1914; 20:433–51.

    Google Scholar 

  • McCay CM, Crowell MF. 1934. Prolonging the life span. Sci. Mon. 39:405–14.

    Google Scholar 

  • Tannenbaum A. 1944. The dependence of the genesis of induced skin tumors on the caloric intake during different stages of carcinogenesis. Cancer Res. 4:673–79.

    Google Scholar 

  • Hursting, S.D., Lavigne, J.A., Berrigan, D., Perkins, S.N. and Barrett, J.C. (2003) Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu Rev Med, 54:131–52.

    Google Scholar 

  • Hursting SD, Smith SM, Lashinger LM, Harvey AE, Perkins SN. Calorie restriction and Carcinogenesis: Lessons learned from 30 years of research. Carcinogenesis 2010; 31:83–9.

    Google Scholar 

  • Colman, R.J., Anderson, R.M., Johnson, S.C., Kastman, E.K., Kosmatka, K.J., Beasley, T.M., Allison, D.B., Cruzen, C., Simmons, H.A., Kemnitz, J.W. and Weindruch, R. (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325, 201–4.

    Google Scholar 

  • Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 2010 303:235–41.

    Google Scholar 

  • Ogden CL, Fryar CD, Carroll MD, Flegal KM. Mean body weight, height, and body mass index, United States 1960–2002. Advance data from vital and health statistics; no 347. Hyattsville, Maryland: National Center for Health Statistics. 2004.

    Google Scholar 

  • Calle, E.E., Rodriguez, C., Walker-Thurmond, K. and Thun, M.J. (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med, 348, 1625–38.

    Google Scholar 

  • Hursting SD, Lashinger LM, Wheatley KW, Rogers CJ, Colbert LH, Nunez, NP, Perkins SN. Reducing the weight of cancer: Mechanistic targets for breaking the obesity-carcinogenesis link. Best Pract Res Clin Endocrinol Metab, 2008, 22:659–669.

    Google Scholar 

  • Yakar, S., Leroith, D. and Brodt, P. (2005) The role of the growth hormone/insulin-like growth factor axis in tumor growth and progression: Lessons from animal models. Cytokine Growth Factor Rev, 16, 407–20.

    Google Scholar 

  • Sara, V.R. and Hall, K. (1990) Insulin-like growth factors and their binding proteins. Physiol Rev, 70, 591–614.

    Google Scholar 

  • Ma QL, Tang TL, Yin JY, Peng ZY, Yu M, Liu ZQ, Chen FP. Role of insulin-like growth factor-1 in regulating cell cycle progression. Biochem Biophys Res Comm 2009; 389:150–5.

    Google Scholar 

  • LeRoith, D., Baserga, R., Helman, L. and Roberts, C.T., Jr. (1995) Insulin-like growth factors and cancer. Ann Intern Med, 122, 54–9.

    Google Scholar 

  • Resnicoff, M., Abraham, D., Yutanawiboonchai, W., Rotman, H.L., Kajstura, J., Rubin, R., Zoltick, P. and Baserga, R. (1995) The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo. Cancer Res, 55, 2463–9.

    Google Scholar 

  • Pollak, M. (2008) Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer, 8, 915–28.

    Google Scholar 

  • Rogers CJ, Colbert LH, Berrigan D, Greiner JW, Perkins SN, Hursting SD. Physical activity and cancer prevention: Pathways and targets for intervention. Sports Medicine 2008; 38(4): 221–57.

    Google Scholar 

  • McTiernan A, Sorensen B, Yasui Y, Tworoger SS, Ulrich CM, Irwin ML, Rudolph RE, Stanczyk FZ, Schwartz RS, Potter JD. No effect of exercise on insulin-like growth factor-1 and ­insulin-like binding protein 3 in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol Biomarkers Prev 14:1020, 2005.

    Google Scholar 

  • Koistinen H, Koistinen R, et al. Effect of marathon run on serum IGF-1 and IGF-binding protein 1 and 3 levels. J Appl Physiol 1996; 80(3): 760–4.

    Google Scholar 

  • Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab 2006; 17:328–36.

    Google Scholar 

  • Sandhu MS, Dunger DB, Giovannucci EL. Insulin, insulin-like growth factor, IGF binding proteins, their biologic interactions, and colorectal cancer. JNCI 2002; 94:972–80.

    Google Scholar 

  • Luo, J., Manning, B. D., and Cantley, L. C. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell, 4: 257–62, 2003.

    Google Scholar 

  • Engelman, J. A., Luo, J., and Cantley, L. C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet, 7: 606–19, 2006.

    Google Scholar 

  • Shaw, R. J., and Cantley, L. C. Ras, PI(3)K and mTOR signaling controls tumor cell growth. Nature, 441: 424–30, 2006.

    Google Scholar 

  • Brazil, D. P., Yang, Z. Z., and Hemmings, B. A. Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci, 29: 233–42, 2004.

    Google Scholar 

  • Dillon RL, Muller WJ. Distinct biological roles for the AKt family in mammary tumor progression. Cancer Res 2010; 70:426064.

    Google Scholar 

  • Hay, N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell, 8: 179–83, 2005.

    Google Scholar 

  • Sarbassov DD, Sabatini DM. Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complex. J Biol Chem 2005; 280: 39505–39509.

    Google Scholar 

  • Guertin, D.A. and D.M. Sabatini, An expanding role for mTOR in cancer. Trends Mol Med, 2005. 11(8): p. 353–61.

    Google Scholar 

  • Kwiatkowki DJ, Manning BD. Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genetics 2005; 14:R251-8.

    Google Scholar 

  • Moore T, Beltran L, Carbijal S, Strom S, Traag J, Hursting SD, DiGiovanni J, Dietary energy balance modulates signaling through the Akt/mTOR pathway in multiple tissues. Cancer Prev Res 2008; 1:65–76.

    Google Scholar 

  • Jiang, W., Z. Zhu, Thompson H. Dietary energy restriction modulates the activity of amp-activated protein kinase, akt, and mammalian target of rapamycin in mammary carcinomas, mammary gland, and liver. cancer research, 2008. 68: p. 5492–5499.

    Google Scholar 

  • Moore T, Carbijal S., Beltran L, Perkins SN, Hursting SD, DiGiovanni J, Reduced susceptibility to two-stage skin carcinogenesis in mice with low circulating IGF-1 levels. Cancer Res, 2008. 68: p. 3680–8.

    Google Scholar 

  • The Endogenous Hormones and Breast Cancer Collaborative Group. Insulin-like growth factor-q (IGF1), IGF binding protein 3 (IGFBP3) and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncology 11:530–42, 2010.

    Google Scholar 

  • Chan JM, Stampfer MJ, Giovannucci E, et al. 1998. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 279:563–66.

    Google Scholar 

  • Wolk A, Mantzoros CS, Andersson SO, et al. 1998. Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study. J. Natl. Cancer Inst. 90:911–15.

    Google Scholar 

  • Yu H, Spitz MR, Mistry J, et al. 1999. Plasma levels of insulin-like growth factor--I and lung cancer risk: a case-control analysis. J. Natl. Cancer Inst. 91:151–56.

    Google Scholar 

  • Ma J, Pollak MN, Giovannucci E, et al. 1999. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J. Natl. Cancer Inst. 91:620–25.

    Google Scholar 

  • Giovannucci E, Pollak MN, Platz EA, et al. 2000. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol. Biomarkers Prev. 9:345–49.

    Google Scholar 

  • Petridou E, Dessypris N, Spanos E, et al. 1999. Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia. Int. J. Cancer 80:494–96.

    Google Scholar 

  • Douglas JB, Silverman DT, Pollak MN, Tao Y, Soliman AS, Stolzenberg-Solomon R. Serum IGF-1, IGF-II, IGFBP-3 and IGF-1/BP-3 molar ratio and risk of pancreatic cnacer in the PLCO cancer screening trial. Cancer Epidemiol Biomarkers Prev 2010; 19:2298–306.

    Google Scholar 

  • Macaulay, V.M. (1992) Insulin-like growth factors and cancer. Br J Cancer, 65, 311–20.

    Google Scholar 

  • Flurkey K, Papaconstantinou J, Miller RA, Harrison DE. 2001. Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc. Natl. Acad. Sci. USA 98:6736–41.

    Google Scholar 

  • Bartke A, Brown-Borg HM. Life extension in the dwarf mouse. Curr Topics Dev Biol 2004; 63:189–225.

    Google Scholar 

  • Anisimov VN. 2001. Mutant and genetically modified mice as models for studying the relationship between aging and carcinogenesis. Mech. Ageing Dev. 122:1221–55.

    Google Scholar 

  • DiGiovanni J, Bol DK, Wilker E, et al. 2000. Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion. Cancer Res. 60:1561–70.

    Google Scholar 

  • Hursting SD, Perkins SN, Lavigne JA, Beltran L, Haines DC, Hill HL, Alvord WG, Barrett JC, DiGiovanni J. Urothelial overexpression of insulin-like growth factor-1 increases susceptibility to p-Cresidine-induced bladder carcinogenesis in transgenic mice. Mol Carcinogenesis 2009; 48:671–7.

    Google Scholar 

  • Yiping Wu, Karen Cui, Keiko Miyoshi, Lothar Hennighausen, Jeffrey E. Green, Jennifer Setser, Derek LeRoith, Shoshana Yakar. Reduced Circulating Insulin-like Growth Factor I Levels Delay the Onset of Chemically and Genetically Induced Mammary Tumors. Cancer Res 2003; 63:4384–88.

    Google Scholar 

  • Olivo-Marston S, Hursting SD, Lavigne J, Perkins SN, Marouf R, Yakar S, Harris CC. Genetic reduction of insulin-like growth factor-1 inhibits azoxymethane-induced colon tumorigenesis in mice. Mol Carcinogenesis 2009, 48:1071–6.

    Google Scholar 

  • Lashinger LM, Malone LM, McArthur MJ, Goldberg JA, Daniels EA, Pavone A, Colby JK, Perkins SN, Fischer SM, Hursting SD. Genetic reduction of insulin-like growth factor-1 mimics the anticancer effects of calorie restriction on cyclooxygenase-2-drive pancreatic cancer. Cancer Prev Res 2010; in press.

    Google Scholar 

  • Polunovsky V and Houghton PJ (2010). mTOR pathway and mTOR inhibitors in cancer therapy. New York, NY: Humana Press.

    Google Scholar 

  • Wu Y, Brodt P, Sun H, Mejia W, Novosyadlyy R, Nunez N, Chen X, Mendoza A, Hong SH, Khanna C, Yakar S. Insulin-like growth factor-I regulates the liver microenvironment in obese mice and promotes liver metastasis Cancer Res 70: 57–67, 2010.

    Google Scholar 

  • Fagan DH, Yee D. Crosstalk between IGF1R and estrogen receptor signaling in breast cancer. J Mammary Gland Biol Neoplasia. 2008; 13: 423–9.

    Google Scholar 

  • Mawson A, Lai A, Carroll JS, Sergio CM, Mitchell CJ, and Sarcevic B. Estrogen and insulin/IGF-1 cooperatively stimulate cell cycle progression in MCF-7 breast cancer cells through differential regulation of c-Myc and cyclin D1. Mol Cell Endocrinol 2005; 229(1–2): 161–73.

    Google Scholar 

  • Sachdev D and Yee D. The IGF system and breast cancer. Endocr Relat Cancer 2001; 8(3):197–209.

    Google Scholar 

  • Saxena NK, Taliaferro-Smith L, Knight BB, Merlin D, Anania FA, O’Regan RM, and Sharma D. Bidirectional crosstalk between leptin and insulin-like growth factor-I signaling promotes invasion and migration of breast cancer cells via transactivation of epidermal growth factor receptor. Cancer Res 2008; 68(23): 9712–22.

    Google Scholar 

  • Ozbay T and Nahta R. A novel unidirectional cross-talk from the insulin-like growth factor-I receptor to leptin receptor in human breast cancer cells. Mol Cancer Res 2008; 6(6): 1052–8.

    Google Scholar 

  • Balañá ME, Labriola L, Salatino M, Movsichoff F, Peters G, Charreau EH, and Elizalde PV. Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insulin-like growth factor receptor in mammary tumor cells. Oncogene 2001; 20(1): 34–47.

    Google Scholar 

  • Shida D, Kitayama J, Mori K, Watanabe T and Nagawa H. Transactivation of epidermal growth factor receptor is involved in leptin-induced activation of janus-activated kinase 2 and extracellular signal-regulated kinase 1/2 in human gastric cancer cells. Cancer Res 2005; 65(20): 9159–63.

    Google Scholar 

  • Hursting SD, Lashinger LM, Colbert LH, Rogers CJ, Wheatley KW, Nunez NP, Mahabir S, Barrett JC, Forman MR, and Perkins SN. Energy balance and carcinogenesis: underlying pathways and targets for intervention. Curr Cancer Drug Targets 2007; 7(5): 484–91.

    Google Scholar 

  • Mitsiades CS, Mitsiades N, Poulaki V, Schlossman R, Akiyama M, Chauhan D, Hideshima T, Treon SP, Munshi NC, Richardson PG, and Anderson KC. Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications. Oncogene 2002; 21(37): 5673–83.

    Google Scholar 

  • Fenton JI, Birmingham JM, Hursting SD, and Hord NG. Adiponectin blocks multiple signaling cascades associated with leptin-induced cell proliferation in Apc Min/+ colon epithelial cells. Int J Cancer 2008; 122(11): 2437–45.

    Google Scholar 

  • Fang J, Zhou Q, Shi XL, Jiang BH. Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells. Carcinogenesis 2007; 28(3): 713–23.

    Google Scholar 

  • Garafalo C and Surmacz E. Leptin and cancer. Cell Phys 2005; 207:12–22.

    Google Scholar 

  • Sachdev D and Yee D. Disrupting insulin-like growth factor signaling as a potential cancer therapy. Mol Cancer Therap 2007; 6:1–12.

    Google Scholar 

  • Eng-Wong J, Hursting SD, Perkins SN, Zujewski J. Effects of raloxifene on insulin-like growth factor (IGF)-1, IGF-binding protein-3 and leptin in premenopausal women at high risk for breast cancer. Cancer Epidemiol Biomarkers Prev 2003; 12:1468–73.

    Google Scholar 

  • Lubet RA, Christov K, Nunez N, Hursting SD, Steele VE, Juliana MM, Eto I, Grubbs CJ. Effects of the RXR agonist targretin in the methylnitrosourea-induced mammary cancer model: Dose response curves, cancer cell proliferation and apoptosis, and serum IGF-1 levels. Carcinogenesis 2005; 26:441–8.

    Google Scholar 

  • DeAngel RD, Smith SD, Perkins SN, Glickman R, Hursting SD. Anti-tumor effects of ursolic acid in a mouse model of postmenopausal breast cancer. Nutr Cancer 2010; in press.

    Google Scholar 

  • Fang J. Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells. Carcinogenesis 2006; 28:713–23.

    Google Scholar 

  • Anand P, Sundaram C, et al. Curcumin and Cancer: an “old-age” disease with an “age-old” solution. Cancer Letters 2008; 267(1): 133–64.

    Google Scholar 

  • Harrison, D.E., Strong, R., Sharp, Z.D., Nelson, J.F., Astle, C.M., Flurkey, K., Nadon, N.L., Wilkinson, J.E., Frenkel, K., Carter, C.S., Pahor, M., Javors, M.A., Fernandez, E. and Miller, R.A. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature, 460, 392–5.

    Google Scholar 

  • Sahra IB, et al. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease in cyclin D1 levels. Oncogene 2008; 27:3576–3586.

    Google Scholar 

  • Hardie DG. AMPK: A key regulator of energy balance in the single cell and the whole organism. Int J Obes 2008; 32:S7–12.

    Google Scholar 

  • Memmott RM, et al. Metformin prevents tobacco carcinogen-induced lung tumorigenesis. Cancer Prevention Res 2010; 3:1066–76.

    Google Scholar 

  • Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. 2009;32(9):1620–5. PMCID: 2732153.

    Google Scholar 

  • Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009;137(2):482–8.

    Google Scholar 

  • Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009;27(20):3297–302.

    Google Scholar 

  • Hosono et al. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prevention Res 2010; 3:1077–83.

    Google Scholar 

  • Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res 2010; 3:1060–65.

    Google Scholar 

  • Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., Hahn, W.C., Guarente, L.P. and Sinclair, D.A. (2008) The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One, 3, e2020.S.

    Google Scholar 

  • Signorelli, P. and Ghidoni, R. (2005) Resveratrol as an anticancer nutrient: molecular basis, open questions and promises. J Nutr Biochem, 16, 449–66.

    Google Scholar 

  • Liu, T., Liu, P.Y. and Marshall, G.M. (2009) The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res, 69, 1702–5.

    Google Scholar 

  • Kalaany NY, Sabatini DM. Tumours with PI3K activation are resistant to dietary restriction. Nature 2009; 458:725–31.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen D. Hursting .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hursting, S.D., Smith, S.D., Harvey, A.E., Lashinger, L.M. (2012). Calories and Cancer: The Role of Insulin-Like Growth Factor-1. In: LeRoith, D. (eds) Insulin-like Growth Factors and Cancer. Cancer Drug Discovery and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0598-6_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-0598-6_12

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4614-0597-9

  • Online ISBN: 978-1-4614-0598-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics