, Volume 3, Issue 2, pp 66–71 | Cite as

La leptine: un lien entre obésité et cancer du sein

  • J. -P. PeyratEmail author
  • F. Révillion
  • J. Grosjean
  • M. Charlier
  • J. Djiane
Dossier Thématique / Thematic File


Les liens entre obésité et cancer du sein pourraient résulter de l’action d’adipokines produites par les cellules adipeuses. Parmi ces adipokines, la leptine semble jouer un rôle important. La présence de ses récepteurs sur les cellules de cancers du sein montre qu’elle peut agir directement sur ces cellules: elle est de fait capable de stimuler leur prolifération. Les voies d’action empruntées sont endocrine, paracrine et autocrine. De plus, la leptine serait capable de s’opposer aux traitements anti-estrogéniques. Ces observations suggèrent que le blocage de la leptine aurait un intérêt thérapeutique dans les cancers du sein.

Mots clés

Leptine Obésité Cancer du sein 

Leptin: a link between obesity and breast cancer


Links between obesity and breast cancer could result from the action of adipokines produced by adipocytes. Among these adipokines, leptin appears to have an important role. The presence of its receptors on breast cancer cells shows that it can act directly on these cells: it is able to stimulate their proliferation. There are three distinct modes of action through endocrine-, paracrine-, and autocrine-mediated pathways. Moreover, leptin would appear to be able to counteract anti-estrogenic treatments. These observations suggest that it could be of therapeutic interest to target leptin in breast cancer.


Leptin Obesity Breast cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Key TJ, Appleby PN, Reeves GK, et al. (2003) Endogenous Hormones Breast Cancer Collaborative Group. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95: 1218–1226PubMedCrossRefGoogle Scholar
  2. 2.
    Van den Brandt PA, Spiegelman D, Yaun SS, et al. (2000) Pooled analysis of prospective cohort studies on height, weight and breast cancer risk. Am J Epidemiol 152: 514–527PubMedCrossRefGoogle Scholar
  3. 3.
    Porter GA, Inglis KM, Wood LA, Veugelers PJ (2006) Effect of obesity on presentation of breast cancer. Ann Surg Oncol 13: 327–332PubMedCrossRefGoogle Scholar
  4. 4.
    Zhang Y, Proence R, Maffei M, et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425–432PubMedCrossRefGoogle Scholar
  5. 5.
    Rose DP, Gilhooly EM, Nixon DW (2002) Adverse effects of obesity on breast cancer prognosis, and the biological actions of leptin (review). Int J Oncol 21: 1285–1292PubMedGoogle Scholar
  6. 6.
    Dieudonne MN, Machinal-Quelin F, Serazin-Leroy V, et al. (2002) Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun 293: 622–628PubMedCrossRefGoogle Scholar
  7. 7.
    Hu X, Juneja SC, Maihle NJ, Cleary MP (2002) Leptin: a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst 94: 1704–1711PubMedGoogle Scholar
  8. 8.
    Laud K, Gourdou I, Pessemesse L, et al. (2002) Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. Mol Cell Endocrinol 188: 219–226PubMedCrossRefGoogle Scholar
  9. 9.
    Garofalo C, Surmacz E (2006) Leptin and cancer. J Cell Physiol 207(1): 12–22PubMedCrossRefGoogle Scholar
  10. 10.
    Frankenberry KA, Skinner H, Somasundar P, et al. (2006) Leptin receptor expression and cell signaling in breast cancer. Int J Oncol 28: 985–993PubMedGoogle Scholar
  11. 11.
    Chen C, Chang YC, Liu CL, et al. (2006) Leptin-induced growth of human ZR-75-1 breast cancer cells is associated with up-regulation of cyclin D1 and c-Myc and down-regulation of tumor suppressor p53 and p21WAF1/CIP1. Breast cancer Res Treat 98: 121–132PubMedCrossRefGoogle Scholar
  12. 12.
    Catalano S, Mauro L, Marsico S, et al. (2004) Leptin induces, via ERK1/ERK2 signal, functional activation of estrogen receptor alpha in MCF-7 cells. J Biol Chem 279: 19908–19915PubMedCrossRefGoogle Scholar
  13. 13.
    Catalano S, Marsico S, Giordano, et al. (2003) Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line. J Biol Chem 278: 28668–28676PubMedCrossRefGoogle Scholar
  14. 14.
    Garofalo C, Sisci D, Surmacz E (2004) Leptin interferes with the effects of the anti-estrogen ICI 182,780 in MCF-7 breast cancer cells. Clin Cancer Res 10: 6466–6475PubMedCrossRefGoogle Scholar
  15. 15.
    O’Brien SN, Welter BH, Price TM (1999) Presence of leptin in breast cell lines and breast tumors. Biochem Biophys Res Commun 259: 695–698PubMedCrossRefGoogle Scholar
  16. 16.
    Cleary MP, Phillips FC, Getsin SC, et al. (2003) Genetically obese MMTV-TGF-alpha/Lep(ob)Lep(ob) female mice do not develop mammary tumors. Breast Cancer Res Treat 77: 205–215PubMedCrossRefGoogle Scholar
  17. 17.
    Cleary MP, Juneja SC, Phillips FC, et al. (2004) Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors. Exp Biol Med 229: 182–193Google Scholar
  18. 18.
    Goodwin PJ, Ennis M, Fantus IG, et al. (2005) Is leptin a mediator of adverse prognostic effects of obesity in breast cancer? J Clin Oncol 23: 6037–6042PubMedCrossRefGoogle Scholar
  19. 19.
    Tessitore L, Vizio B, Jenkins O, et al. (2000) Leptin expression in colorectal and breast cancer patients. Int J Mol Med 5: 421–426PubMedGoogle Scholar
  20. 20.
    Han C, Zhang HT, Du L, et al. (2005) Serum levels of leptin, insulin, and lipids in relation to breast cancer in china. Endocrine 26: 19–24PubMedCrossRefGoogle Scholar
  21. 21.
    Chen DC, Chung YF, Yeh YT, et al. (2006) Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett 237: 109–114PubMedCrossRefGoogle Scholar
  22. 22.
    Falk RT, Brinton LA, Madigan MP, et al. (2006) Interrelationships between serum leptin, IGF-1, IGFBP3, C-peptide and prolactin and breast cancer risk in young women. Breast Cancer Res Treat 98: 157–165PubMedCrossRefGoogle Scholar
  23. 23.
    Petridou E, Papadiamantis Y, Markopoulos C, et al. (2000) Leptin and insulin growth factor I in relation to breast cancer (Greece). Cancer Causes Control 11: 383–388PubMedCrossRefGoogle Scholar
  24. 24.
    Ozet A, Arpaci F, Yilmaz MI, et al. (2001) Effects of tamoxifen on the serum leptin level in patients with breast cancer. Jpn J Clin Oncol 31: 424–427PubMedCrossRefGoogle Scholar
  25. 25.
    Coskun U, Günel N, Toruner FB, et al. (2003) Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer. Neoplasma 50: 41–46PubMedGoogle Scholar
  26. 26.
    Sauter ER, Garofalo C, Hewett J, et al. (2004) Leptin expression in breast nipple aspirate fluid (NAF) and serum is influenced by body mass index (BMI) but not by the presence of breast cancer. Horm Metab Res 36: 336–340PubMedCrossRefGoogle Scholar
  27. 27.
    Miyoshi Y, Funahashi T, Tanaka S, et al. (2006) High expression of leptin receptor mRNA in breast cancer tissue predicts poor prognosis for patients with high, but not low, serum leptin levels. Int J Cancer 118: 1414–1419PubMedCrossRefGoogle Scholar
  28. 28.
    Woo HY, Park H, Ki CS, et al. (2006) Relationships among serum leptin, leptin receptor gene polymorphisms, and breast cancer in Korea. Cancer Lett 237: 137–142PubMedCrossRefGoogle Scholar
  29. 29.
    Stattin P, Söderberg S, Biessy C, et al. (2004) Plasma leptin and breast cancer risk: a prospective study in northern Sweden. Breast Cancer Res Treat 86: 191–196PubMedCrossRefGoogle Scholar
  30. 30.
    Cento RM, Proto C, Spada RS, et al. (1999) Leptin levels in menopause: effect of estrogen replacement therapy. Horm Res 52: 269–273PubMedCrossRefGoogle Scholar
  31. 31.
    Hayase H, Nomura S, Abe T, Izawa T (2002) Relation between fat distributions and several plasma adipocytokines after exercise training in premenopausal and post-menopausal women. J Physiol Anthropol Appl Human Sci 21: 105–113PubMedCrossRefGoogle Scholar
  32. 32.
    Caprio M, Fabbrini E, Isidori AM, et al. (2001) Leptin in reproduction. Trends Endocrinol Metab 12: 65–72PubMedCrossRefGoogle Scholar
  33. 33.
    Messinis IE, Papageorgiou I, Milingos S, et al. (2001) Estradiol plus progesterone treatment increases serum leptin concentrations in normal women. Hum Reprod 16: 1827–1832PubMedCrossRefGoogle Scholar
  34. 34.
    Tartaglia LA, Dembski M, Weng X, et al. (1995) Identification and expression cloning of a leptin receptor, OB-R. Cell 83: 1263–1271PubMedCrossRefGoogle Scholar
  35. 35.
    Barr VA, Lane K, Taylor SI (1999) Subcellular localization and internalization of the four human leptin receptor isoformes. J Biol Chem 274: 21416–21424PubMedCrossRefGoogle Scholar
  36. 36.
    Tartaglia LA (1997) The leptin receptor. J Biol Chem 272: 6093–6096PubMedGoogle Scholar
  37. 37.
    Winick JD, Stoffel M, Friedman JM (1996) Identification of microsatellite markers linked to the human leptin receptor gene on chromosome 1. Genomics 36: 221–222PubMedCrossRefGoogle Scholar
  38. 38.
    Bjorbaek C, Uotani S, da Silva B, Flier JS (1997) Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem 272: 32686–32695PubMedCrossRefGoogle Scholar
  39. 39.
    Yamashita T, Murakami T, Otani S, et al. (1998) Leptin receptor signal transduction: OBRa and OBRb of fa type. Biochem Biophys Res Commun 246: 752–759PubMedCrossRefGoogle Scholar
  40. 40.
    Sinha MK, Poentanova I, Ohannesian JP, et al. (1996) Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest 98: 1277–1282PubMedCrossRefGoogle Scholar
  41. 41.
    Brabant G, Nave H, Mayr B, et al. (2002) Secretion of free and protein-bound leptin from subcutaneous adipose tissue of lean and obese women. J Clin Endocrinol Metab 87: 3966–3970PubMedCrossRefGoogle Scholar
  42. 42.
    Maamra M, Bidlingmaier M, Postel-Vinay MC, et al. (2001) Generation of human soluble leptin receptor by proteolytic cleavage of membrane-anchored receptors. Endocrinology 142: 4389–4393PubMedCrossRefGoogle Scholar
  43. 43.
    Ge H, Huang L, Pourbahrami T, Li C (2002) Generation of soluble leptin receptor by ectodomain shedding of membrane-spanning receptors in vitro and in vivo. J Biol Chem 277: 45898–45903PubMedCrossRefGoogle Scholar
  44. 44.
    Révillion F, Charlier M, Lhotellier V, et al. (2006) Messenger RNA expression of leptin and leptin receptors and their prognostic value in human primary breast cancer. Clin Cancer Res 12: 2088–2094PubMedCrossRefGoogle Scholar
  45. 45.
    Ishikawa M, Kitayama J, Nagawa H (2004) Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res 10: 4325–4331PubMedCrossRefGoogle Scholar
  46. 46.
    Tessitore L, Vizio B, Pesola D, et al. (2004) Adipocyte expression and circulating levels of leptin increase in both gynaecological and breast cancer patients. Int J Oncol 24: 1529–1535PubMedGoogle Scholar
  47. 47.
    Révillion F, Bonneterre J, Peyrat JP (1998) ERBB2 oncogene in human breast cancer and its clinical significance. Eur J Cancer 34: 791–808PubMedCrossRefGoogle Scholar
  48. 48.
    Pawlowski V, Révillion F, Hebbar M, et al. (2000) Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res 6: 4217–4225PubMedGoogle Scholar
  49. 49.
    Eisenberg A, Biener E, Charlier M, et al. (2004) Transactivation of erbB2 by short and long isoforms of leptin receptors. FEBS Lett 565: 139–142PubMedCrossRefGoogle Scholar
  50. 50.
    Soma D, Kitayama J, Yamashita H, et al. (2007) Leptin augments proliferation of breast cancer cells via transactivation of HER2. J Surg Res. [Epub ahead of print]Google Scholar
  51. 51.
    Hoffstedt J, Eriksson P, Mottagui-Tabar S, Arner P (2002) A polymorphism in the leptin promoter region (−2548 G/A) influences gene expression and adipose tissue secretion of leptin. Horm Metab Res 34: 355–359PubMedCrossRefGoogle Scholar
  52. 52.
    Mammès O, Betoulle D, Aubert R, et al. (1998) Novel polymorphisms in the 5′ region of the LEP gene: association with leptin levels and response to low calorie diet in human obesity. Diabetes 47: 487–489PubMedCrossRefGoogle Scholar
  53. 53.
    Li WD, Reed DR, Lee JH, et al. (1999) Sequence variants in the 5′ flanking region of the leptin gene are associated with obesity in women. Ann Hum Genet 63: 227–234PubMedCrossRefGoogle Scholar
  54. 54.
    Wang TN, Huang TN, Chang WT, et al. (2006) G-2548A polymorphism of the leptin gene is correlated with extreme obesity in Taiwanese aborigines. Obesity 14: 183–187PubMedCrossRefGoogle Scholar
  55. 55.
    Mammès O, Aubert R, Betoulle D, et al. (2001) LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women. Eur J Clin Invest 31: 398–404PubMedCrossRefGoogle Scholar
  56. 56.
    Yiannakouris N, Yannakoulia M, Melistas L, et al. (2001) The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J Clin Endocrinol Metab 86: 4434–4439PubMedCrossRefGoogle Scholar
  57. 57.
    Duarte SF, Francischetti EA, Genelhu-Abreu V, et al. (2006) p.Q223R leptin receptor polymorphism associated with obesity in Brazilian multi-ethnic subjects. Am J Hum Biol 18: 448–453PubMedCrossRefGoogle Scholar
  58. 58.
    Snoussi K, Strosberg AD, Bouaouina N, et al. (2006) Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma. BMC Cancer 6: 38PubMedCrossRefGoogle Scholar
  59. 59.
    Liu CL, Chang YC, Cheng SP, et al. (2007) The roles of serum leptin concentration and polymorphism in leptin receptor gene at codon 109 in breast cancer. Oncology 72: 75–81PubMedCrossRefGoogle Scholar
  60. 60.
    Vona-Davis L, Rose DP (2007) Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer 14(2): 189–206PubMedCrossRefGoogle Scholar
  61. 61.
    Surmacz E (2007) Obesity hormone leptin: a new target in breast cancer? Breast Cancer Res 9: 301PubMedGoogle Scholar

Copyright information

© Springer Paris 2008

Authors and Affiliations

  • J. -P. Peyrat
    • 1
    Email author
  • F. Révillion
    • 1
  • J. Grosjean
    • 1
    • 2
  • M. Charlier
    • 3
  • J. Djiane
    • 3
  1. 1.Laboratoire d’oncologie moléculaire humainecentre Oscar-LambretLille cedexFrance
  2. 2.Centre hospitalier de ValenciennesValenciennes cedexFrance
  3. 3.Unité de neuroendocrinologie moléculaire de la prise alimentaireInstitut National de la Recherche AgronomiqueJouy-en-Josas cedexFrance

Personalised recommendations