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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi

CiteScore 2018: 2.43

SCImago Journal Rank (SJR) 2018: 0.947
Source Normalized Impact per Paper (SNIP) 2018: 0.837

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Volume 22, Issue 2


The direct and indirect effects of corticosterone and primary adipose tissue on MCF7 breast cancer cell cycle progression

Yaniv Shpilberg
  • School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, ON, Canada
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Michael K. Connor
  • School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, ON, Canada
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Michael C. Riddell
  • Corresponding author
  • School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, ON, Canada
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-04-14 | DOI: https://doi.org/10.1515/hmbci-2015-0003


Background: Breast cancer is the second leading cause of cancer-related mortality in women. Glucocorticoids (GCs) have the potential to directly affect breast cancer or indirectly via changes to the tumor growth microenvironment a breast cancer is exposed to. The role of GCs in breast cancer progression by direct and indirect means are not fully understood.

Aim: To study the direct and indirect effects of GCs on breast cancer cell cycle regulation.

Methods: MCF7 breast cancer cells were incubated with increasing concentrations of corticosterone (CORT) to investigate the direct effects. In addition, MCF7 cells were cultured in conditioned media (CM) from primary adipose tissue excised from CORT-supplemented lean and obese male rats.

Results: CORT alone resulted in dose-dependent increases in p27 and hypophosphorylated retinoblastoma protein (Rb) which was accompanied by a reduction in the number of cells in S-phase. CM prepared from adipose tissue overrode these direct CORT effects, suggesting that the tumor growth microenvironment created in the CM dominates MCF7 cell cycle regulation.

Conclusions: The direct inhibitory effects of CORT on cancer cell cycle progression are largely limited by the hormone’s effects on adipose tissue biology.

Keywords: adipokines; adiponectin; breast cancer; breast neoplasms/drug therapy; corticosterone; glucocorticoid/physiology; leptin; MCF7; receptors; rodents


  • 1.

    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90.Google Scholar

  • 2.

    Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M, Comparative Risk Assessment collaborating group (Cancers). Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet 2005;366:1784–93.Google Scholar

  • 3.

    Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548–56.CrossrefPubMedGoogle Scholar

  • 4.

    Grisouard J, Dembinski K, Mayer D, Keller U, Muller B, Christ-Crain M. Targeting AMP-activated protein kinase in adipocytes to modulate obesity-related adipokine production associated with insulin resistance and breast cancer cell proliferation. Diabetol Metab Syndr 2011;3:16.Web of SciencePubMedCrossrefGoogle Scholar

  • 5.

    Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579–91.PubMedCrossrefGoogle Scholar

  • 6.

    Lee CH, Woo YC, Wang Y, Yeung CY, Xu A, Lam KS. Obesity, adipokines and cancer: an update. Clin Endocrinol (Oxf). 2014. doi: 10.1111/cen.12667. [Epub ahead of print] PubMed PMID: 25393563.CrossrefGoogle Scholar

  • 7.

    Ruzzin J, Wagman AS, Jensen J. Glucocorticoid-induced insulin resistance in skeletal muscles: defects in insulin signalling and the effects of a selective glycogen synthase kinase-3 inhibitor. Diabetologia 2005;48:2119–30.PubMedCrossrefGoogle Scholar

  • 8.

    Peckett AJ, Wright DC, Riddell MC. The effects of glucocorticoids on adipose tissue lipid metabolism. Metabolism 2011;60:1500–10.CrossrefPubMedGoogle Scholar

  • 9.

    Andrew R, Westerbacka J, Wahren J, Yki-Jarvinen H, Walker BR. The contribution of visceral adipose tissue to splanchnic cortisol production in healthy humans. Diabetes 2005;54:1364–70.PubMedCrossrefGoogle Scholar

  • 10.

    Ryan VH, German AJ, Wood IS, Hunter L, Morris P, Trayhurn P. Adipokine expression and secretion by canine adipocytes: stimulation of inflammatory adipokine production by LPS and TNFalpha. Pflugers Arch 2010;460:603–16.Web of ScienceGoogle Scholar

  • 11.

    Shi JH, Du WH, Liu XY, Fan YP, Hu XL, Zhou HY, Xu HB, Zhang XM, Xiang P, Chen FL. Glucocorticoids decrease serum adiponectin level and WAT adiponectin mRNA expression in rats. Steroids 2010;75:853–8.Web of SciencePubMedCrossrefGoogle Scholar

  • 12.

    Considine RV, Nyce MR, Kolaczynski JW, Zhang PL, Ohannesian JP, Moore JH Jr, Fox JW, Caro JF. Dexamethasone stimulates leptin release from human adipocytes: unexpected inhibition by insulin. J Cell Biochem 1997;65:254–8.PubMedCrossrefGoogle Scholar

  • 13.

    Degawa-Yamauchi M, Moss KA, Bovenkerk JE, Shankar SS, Morrison CL, Lelliott CJ, Vidal-Puig A, Jones R, Considine RV. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor alpha. Obes Res 2005;13:662–9.CrossrefGoogle Scholar

  • 14.

    Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R. Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2002;290:1084–9.Google Scholar

  • 15.

    Rentsch J, Chiesi M. Regulation of ob gene mRNA levels in cultured adipocytes. FEBS Lett 1996;379:55–9.Google Scholar

  • 16.

    Slieker LJ, Sloop KW, Surface PL, Kriauciunas A, LaQuier F, Manetta J, Bue-Valleskey J, Stephens TW. Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem 1996;271:5301–4.Google Scholar

  • 17.

    Lippman M, Bolan G, Huff K. The effects of glucocorticoids and progesterone on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 1976;36:4602–9.PubMedGoogle Scholar

  • 18.

    Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H, Anai M, Onishi Y, Ono H, Inukai K, Abe M, Fukushima Y, Kikuchi M, Oka Y, Asano T. Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells. Diabetes 2002;51:1737–44.CrossrefPubMedGoogle Scholar

  • 19.

    Vicennati V, Vottero A, Friedman C, Papanicolaou DA. Hormonal regulation of interleukin-6 production in human adipocytes. Int J Obes Relat Metab Disord 2002;26:905–11.PubMedGoogle Scholar

  • 20.

    Sewter CP, Digby JE, Blows F, Prins J, O’Rahilly S. Regulation of tumour necrosis factor-alpha release from human adipose tissue in vitro. J Endocrinol 1999;163:33–8.Google Scholar

  • 21.

    Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998;83:847–50.Google Scholar

  • 22.

    Perks CM, Holly JM. Hormonal mechanisms underlying the relationship between obesity and breast cancer. Endocrinol Metab Clin North Am 2011;40:485–507, vii.CrossrefWeb of ScienceGoogle Scholar

  • 23.

    Jarde T, Perrier S, Vasson MP, Caldefie-Chezet F. Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer 2011;47:33–43.PubMedCrossrefGoogle Scholar

  • 24.

    Schaffler A, Scholmerich J, Buechler C. Mechanisms of disease: adipokines and breast cancer – endocrine and paracrine mechanisms that connect adiposity and breast cancer. Nat Clin Pract Endocrinol Metab 2007;3:345–54.Web of SciencePubMedCrossrefGoogle Scholar

  • 25.

    Rutz HP. Effects of corticosteroid use on treatment of solid tumours. Lancet 2002;360:1969–70.Google Scholar

  • 26.

    Lee MJ, Wang Y, Ricci MR, Sullivan S, Russell CD, Fried SK. Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue. Am J Physiol Endocrinol Metab 2007;292:E858–64.Web of ScienceGoogle Scholar

  • 27.

    Kanu A, Fain JN, Bahouth SW, Cowan GS, Jr. Regulation of leptin release by insulin, glucocorticoids, G(i)-coupled receptor agonists, and pertussis toxin in adipocytes and adipose tissue explants from obese humans in primary culture. Metabolism 2003;52:60–6.CrossrefPubMedGoogle Scholar

  • 28.

    Buyse M, Viengchareun S, Bado A, Lombes M. Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes. FASEB J 2001;15:1357–66.PubMedCrossrefGoogle Scholar

  • 29.

    Fain JN, Cheema P, Madan AK, Tichansky DS. Dexamethasone and the inflammatory response in explants of human omental adipose tissue. Mol Cell Endocrinol 2010;315:292–8.Google Scholar

  • 30.

    Vaidya JS, Baldassarre G, Thorat MA, Massarut S. Role of glucocorticoids in breast cancer. Curr Pharm Des 2010;16: 3593–3600.CrossrefPubMedGoogle Scholar

  • 31.

    Winokur SH, Baker JJ, Lokey JL, Price NA, Bowen J. Dexamethasone in the treatment of nausea and vomiting from cancer chemotherapy. J Med Assoc Ga 1981;70:263–4.PubMedGoogle Scholar

  • 32.

    Yang N, Zhang H, Si-Ma H, Fu Y, Zhao W, Li D, Yang G. Dexamethasone decreases hepatocellular carcinoma cell sensitivity to cisplatin-induced apoptosis. Hepatogastroenterology 2011;58:1730–5.PubMedGoogle Scholar

  • 33.

    Carter JC, Church FC. Mature breast adipocytes promote breast cancer cell motility. Exp Mol Pathol 2012;92:312–7.CrossrefWeb of SciencePubMedGoogle Scholar

  • 34.

    Inaba H, Pui CH. Glucocorticoid use in acute lymphoblastic leukaemia. Lancet Oncol 2010;11:1096–106.PubMedCrossrefGoogle Scholar

  • 35.

    Doyle SL, Donohoe CL, Lysaght J, Reynolds JV. Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc 2012;71:181–9.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 36.

    Dirat B, Bochet L, Escourrou G, Valet P, Muller C. Unraveling the obesity and breast cancer links: a role for cancer-associated adipocytes? Endocr Dev 2010;19:45–52.Google Scholar

  • 37.

    Yu D, Yu Z, Sun Q, Sun L, Li H, Song J, Mi M, Wu H, Lu L, Liu C, Zhang G, Hu FB, Lin X. Effects of body fat on the associations of high-molecular-weight adiponectin, leptin and soluble leptin receptor with metabolic syndrome in Chinese. PLoS One 2011;6:e16818.CrossrefWeb of ScienceGoogle Scholar

  • 38.

    Mantzoros C, Petridou E, Dessypris N, Chavelas C, Dalamaga M, Alexe DM, Papadiamantis Y, Markopoulos C, Spanos E, Chrousos G, Trichopoulos D. Adiponectin and breast cancer risk. J Clin Endocrinol Metab 2004;89:1102–7.CrossrefPubMedGoogle Scholar

  • 39.

    Ishikawa M, Kitayama J, Nagawa H. Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res 2004;10:4325–31.CrossrefPubMedGoogle Scholar

  • 40.

    Oh SW, Park CY, Lee ES, Yoon YS, Lee ES, Park SS, Kim Y, Sung NJ, Yun YH, Lee KS, Kang HS, Kwon Y, Ro J. Adipokines, insulin resistance, metabolic syndrome, and breast cancer recurrence: a cohort study. Breast Cancer Res 2011;13:R34.PubMedWeb of ScienceCrossrefGoogle Scholar

About the article

Corresponding author: Michael C. Riddell, School of Kinesiology and Health Science, Faculty of Health, York University, 4700 Keele Street, Toronto, ON, Canada, M3J1P3, E-mail:

aMC Riddell and MK Connor share senior authorship.

Received: 2015-01-09

Accepted: 2015-03-02

Published Online: 2015-04-14

Published in Print: 2015-05-01

Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 22, Issue 2, Pages 91–100, ISSN (Online) 1868-1891, ISSN (Print) 1868-1883, DOI: https://doi.org/10.1515/hmbci-2015-0003.

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