Skip to main content

Advertisement

SpringerLink
Log in

Insulin regulates human mammosphere development and function

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Assessing the role of lactogenic hormones in human mammary gland development is limited due to issues accessing tissue samples and so development of a human in vitro three-dimensional mammosphere model with functions similar to secretory alveoli in the mammary gland can aid to overcome this shortfall. In this study, a mammosphere model has been characterised using human mammary epithelial cells grown on either mouse extracellular matrix or agarose and showed insulin is essential for formation of mammospheres. Insulin was shown to up-regulate extracellular matrix genes. Microarray analysis of these mammospheres revealed an up-regulation of differentiation, cell-cell junctions, and cytoskeleton organisation functions, suggesting mammosphere formation may be regulated through ILK signalling. Comparison of insulin and IGF-1 effects on mammosphere signalling showed that although IGF-1 could induce spherical structures, the cells did not polarise correctly as shown by the absence of up-regulation of polarisation genes and did not induce the expression of milk protein genes. This study demonstrated a major role for insulin in mammary acinar development for secretory differentiation and function indicating the potential for reduced lactational efficiency in women with obesity and gestational diabetes.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Australian Institute of Health and Welfare (2019), Australia's Mothers and Babies 2017 ‐ In Brief: AIHW

  • Akhtar N, Marlow R, Lambert E, Schatzmann F, Lowe ET, Cheung J, Katz E, Li W, Wu C, Dedhar S, Naylor MJ, Streuli CH (2009) Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation. Development 136(6):1019–1027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alcaraz J, Nelson C, Bissell M (2004) Biomechanical approaches for studying integration of tissue structure and function in mammary epithelia. J Mammary Gland Biol Neoplasia 9(4):361–374

    Article  PubMed  PubMed Central  Google Scholar 

  • Amir L, Donath S (2007) A systematic review of maternal obesity and breastfeeding intention, initiation and duration. BMC Pregnancy and Childbirth 7(1):9

    Article  PubMed  PubMed Central  Google Scholar 

  • Baker M (2011) Stem cells in culture: defining the substrate. Nat Methods 8(4):293–297

    Article  CAS  Google Scholar 

  • Binas B, Spitzer E, Zschiesche W, Erdmann B, Kurtz A, MÃller, T, Niemann, C, Blenau, W & Grosse, R, (1992) Hormonal induction of functional differentiation and mammary-derived growth inhibitor expression in cultured mouse mammary gland explants. Vitro Cell Dev Biol Anim 28(9):625–634

    Article  Google Scholar 

  • Blatchford D, Wilde C, Matsuda T and Aoki N (2002) Milk secretion in cultured mammary epithelial cells, in Y Kitagawa, T Matsuda & S Iijima (eds). Animal Cell Technology: Basic & Applied Aspects, Springer Netherlands

  • Bolander FJ, Nicholas K, Wyk JV, Topper Y (1981) Insulin is essential for accumulation of casein mRNA in mouse mammary epithelial cells. Proc Natl Acad Sci USA 78(9):5682–5684

    Article  CAS  PubMed  Google Scholar 

  • Bondy CA, Cheng CM (2004) Signaling by insulin-like growth factor 1 in brain. Eur J Pharmacol 490(1–3):25–31

    Article  CAS  PubMed  Google Scholar 

  • Boucher J, Tseng Y-H, Kahn CR (2010) Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. J Biol Chem 285(22):17235–17245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Callaway L, Prins J, Chang A, McIntyre H (2006) The prevalence and impact of overweight and obesity in an Australian obstetric population. Med J Aust 184(2):56–59

    Article  PubMed  Google Scholar 

  • Chapman DJ (2014) Risk factors for delayed lactogenesis among women with gestational diabetes mellitus. Journal of Human Lactation 30(2):134–135

    Article  PubMed  Google Scholar 

  • Cheney K, Farber R, Barratt AL, McGeechan K, de Vries B, Ogle R, Black KI (2018) Population attributable fractions of perinatal outcomes for nulliparous women associated with overweight and obesity, 1990–2014. Med J Aust 208(3):119–125

    Article  PubMed  Google Scholar 

  • Chomczynski P, Qasba P, Topper YJ (1986) Transcriptional and post-transcriptional roles of glucocorticoid in the expression of the rat 25,000 molecular weight casein gene. Biochem Biophys Res Commun 134(2):812–818

    Article  CAS  PubMed  Google Scholar 

  • Clemmons DR (2006) Involvement of insulin-like growth factor-I in the control of glucose homeostasis. Curr Opin Pharmacol 6(6):620–625

    Article  CAS  PubMed  Google Scholar 

  • Cowell JK, LaDuca J, Rossi MR, Burkhardt T, Nowak NJ, Matsui S-i (2005) Molecular characterization of the t(3;9) associated with immortalization in the MCF10A cell line. Cancer Genet Cytogenet 163(1):23–29

    Article  CAS  PubMed  Google Scholar 

  • Cui X, Kim H-J, Kuiatse I, Kim H, Brown PH, Lee AV (2006) Epidermal growth factor induces insulin receptor substrate-2 in breast cancer cells via c-Jun NH2-terminal kinase/activator protein-1 signaling to regulate cell migration. Can Res 66(10):5304–5313

    Article  CAS  Google Scholar 

  • Danoviz M, Yablonka-Reuveni Z (2012) Skeletal muscle satellite cells: background and methods for isolation and analysis in a primary culture system in JX DiMario (ed.). Myogenesis, Humana Press 798:21–52

    Article  CAS  Google Scholar 

  • Debnath J, Brugge JS (2005) Modelling glandular epithelial cancers in three-dimensional cultures. Nat Rev Cancer 5(9):675–688

    Article  CAS  PubMed  Google Scholar 

  • Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS (2002) The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 111(1):29–40

    Article  CAS  PubMed  Google Scholar 

  • Debnath J, Muthuswamy SK, Brugge JS (2003) Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30(3):256–268

    Article  CAS  PubMed  Google Scholar 

  • DiRenzo J, Signoretti S, Nakamura N, Rivera-Gonzalez R, Sellers W, Loda M, Brown M (2002) Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. Can Res 62(1):89–98

    CAS  Google Scholar 

  • Dong Q, Wang D, Bandyopadhyay A, Gao H, Gorena KM, Hildreth K, Rebel VI, Walter CA, Huang C, Sun L-Z (2013) Mammospheres from murine mammary stem cell-enriched basal cells: Clonal characteristics and repopulating potential. Stem Cell Research 10(3):396–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dontu G, Abdallah W, Foley J, Jackson K, Clarke M, Kawamura M, Wicha M (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dupont J, LeRoith D (2001) Insulin and insulin-like growth factor i receptors: similarities and differences in signal transduction , Hormone Research in Paediatrics, vol. 55(suppl 2), no. Suppl 2:22–26

    Google Scholar 

  • Flint DJ, Travers MT, Barber MC, Binart N, Kelly PA (2005) Diet-induced obesity impairs mammary development and lactogenesis in murine mammary gland. American Journal of Endocrinology and metabolism 288(6):E1179–E1187

    Article  CAS  Google Scholar 

  • Gajewska M, Zielniok K, Debski B, Motyl T (2013) IGF-I retards proper development of acinar structures formed by bovine mammary epithelial cells via sustained activation of Akt kinase. Domest Anim Endocrinol 45(3):111–121

    Article  CAS  PubMed  Google Scholar 

  • Garcı́a-Echeverrı́a C, Pearson MA, Marti A, Meyer T, Mestan J, Zimmermann J, Gao J, Brueggen J, Capraro HG, Cozens R, Evans DB, Fabbro D, Furet P, Porta DG, Liebetanz J, Martiny-Baron G, Ruetz S and Hofmann F, (2004) In vivo antitumor activity of NVP-AEW541—a novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell 5(3):231–239

    Article  Google Scholar 

  • Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315

    Article  CAS  PubMed  Google Scholar 

  • Gjorevski N, Nelson CM (2011) Integrated morphodynamic signalling of the mammary gland. Nat Rev Mol Cell Biol 12(9):581–593

    Article  CAS  PubMed  Google Scholar 

  • Hadsell D, Bonnette S (2000) IGF and insulin action in the mammary gland: lessons from transgenic and knockout models. Journal of Mammary Gland Biology and Neoplasia 5(1):19–30

    Article  CAS  PubMed  Google Scholar 

  • Hadsell DL, Olea W, Lawrence N, George J, Torres D, Kadowaki T, Lee AV (2007) Decreased lactation capacity and altered milk composition in insulin receptor substrate null mice is associated with decreased maternal body mass and reduced insulin-dependent phosphorylation of mammary Akt. J Endocrinol 194(2):327–336

    Article  CAS  PubMed  Google Scholar 

  • Hartmann P, Cregan M (2001) Lactogenesis and the effects of insulin-dependent diabetes mellitus and prematurity. The Journal of Nutrition 131(11):3016S-S3020

    Article  CAS  PubMed  Google Scholar 

  • Hovey R, Trott J, Vonderhaar B (2002) Establishing a framework for the functional mammary gland: from endocrinology to morphology. Journal of Mammary Gland Biology and Neoplasia 7(1):17–38

    Article  PubMed  Google Scholar 

  • Hsu E-C, Kulp SK, Huang H-L, Tu H-J, Chao M-W, Tseng Y-C, Yang M-C, Salunke SB, Sullivan NJ, Chen W-C, Zhang J, Teng C-M, Fu W-M, Sun D, Wicha MS, Shapiro CL, Chen C-S (2016) Integrin-linked kinase as a novel molecular switch of the IL-6-NF-κB signaling loop in breast cancer. Carcinogenesis 37(4):430–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ip M, Darcy K (1996) Three-dimensional mammary primary culture model systems. Journal of Mammary Gland Biology and Neoplasia 1(1):91–110

    Article  CAS  PubMed  Google Scholar 

  • Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31(4):e15

    Article  PubMed  PubMed Central  Google Scholar 

  • Jevitt C, Hernandez I, Groër M (2007) Lactation complicated by overweight and obesity: supporting the mother and newborn. Journal of Midwifery and Health 52(6):606–613

    Article  Google Scholar 

  • Khaled WT, Read EKC, Nicholson SE, Baxter FO, Brennan AJ, Came PJ, Sprigg N, McKenzie ANJ, Watson CJ (2007) The IL-4/IL-13/Stat6 signalling pathway promotes luminal mammary epithelial cell development. Development 134(15):2739–2750

    Article  CAS  PubMed  Google Scholar 

  • Korkaya H, Paulson A, Charafe-Jauffret E, Ginestier C, Brown M, Dutcher J, Clouthier SG, Wicha MS (2009) Regulation of mammary stem/progenitor cells by PTEN/Akt/β-catenin signaling. PLoS Biol 7(6):e1000121

    Article  PubMed  PubMed Central  Google Scholar 

  • Kozlowski M, Gajewska M, Majewska A, Jank M and Motyl T (2009) Differences in growth and transcriptomic profile of bovine mammary epithelial monolayer and three-dimensional cell cultures. J Physiol Pharmacol 60(Supp 1):5–14

  • Laviola L, Giorgino F, Chow JC, Baquero JA, Hansen H, Ooi J, Zhu J, Riedel H, Smith RJ (1997) The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF-I receptor in mouse fibroblasts. J Clin Investig 99(5):830–837

    Article  CAS  PubMed  Google Scholar 

  • Lee A, Zhang P, Ivanova M, Bonnette S, Oesterreich S, Rosen J, Grimm S, Hovey R, Vonderhaar B, Kahn C, Torres D, George J, Mohsin S, Allred D, Hadsell D (2003) Developmental and hormonal signals dramatically alter the localization and abundance of insulin receptor substrate proteins in the mammary gland. Endocrinology 144(6):2683–2694

    Article  CAS  PubMed  Google Scholar 

  • Legate KR, Montanez E, Kudlacek O, Fussler R (2006) ILK, PINCH and parvin: the tIPP of integrin signalling. Nat Rev Mol Cell Biol 7(1):20–31

    Article  CAS  PubMed  Google Scholar 

  • Lepe M, Bacardí Gascón M, Castañeda-González LM, Pérez Morales ME, Jiménez Cruz A (2011) Effect of maternal obesity on lactation: systematic review. Nutrición Hospitalaria 26:1266–1269

    CAS  PubMed  Google Scholar 

  • Li ML, Aggeler J, Farson DA, Hatier C, Hassell J, Bissell MJ (1987) Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc Natl Acad Sci 84(1):136–140

    Article  CAS  PubMed  Google Scholar 

  • Mailleux A, Overholtzer M, Brugge J (2008) Lumen formation during mammary epithelial morphogenesis. Insights from in vitro and in vivo models. Cell Cycle 7(1):57–62

    Article  CAS  PubMed  Google Scholar 

  • Menzies K, Lefevre C, Macmillan K, Nicholas K (2009) Insulin regulates milk protein synthesis at multiple levels in the bovine mammary gland. Funct Integr Genomics 9(2):197–217

    Article  CAS  PubMed  Google Scholar 

  • Menzies K, Lee H, Lefèvre C, Ormandy C, Macmillan K, Nicholas K (2010) Insulin, a key regulator of hormone responsive milk protein synthesis during lactogenesis in murine mammary explants. Funct Integr Genomics 10(1):87–95

    Article  CAS  PubMed  Google Scholar 

  • Miousse IR, Gomez-Acevedo H, Sharma N, Vantrease J, Hennings L, Shankar K, Cleves MA, Badger TM, Ronis MJ (2013) Mammary gland morphology and gene expression signature of weanling male and female rats following exposure to exogenous estradiol. Experimental Biology and Medicine 238(9):1033–1046

    Article  PubMed  Google Scholar 

  • Morales J, Alpaugh M (2009) Gain in cellular organization of inflammatory breast cancer: a 3D in vitro model that mimics the in vivo metastasis. BMC Cancer 9(1):462

    Article  PubMed  PubMed Central  Google Scholar 

  • Morrow DA (1976) Fat Cow Syndrome. J Dairy Sci 59(9):1625–1629

    Article  CAS  PubMed  Google Scholar 

  • Moses AC, Young SC, Morrow LA, O’Brien M, Clemmons DR (1996) Recombinant human insulin-like growth factor I increases insulin sensitivity and improves glycemic control in type II diabetes. Diabetes 45(1):91–100

    Article  CAS  PubMed  Google Scholar 

  • Mukhina S, Liu D, Guo K, Raccurt M, Borges-Bendris S, Mertani HC, Lobie PE (2006) Autocrine growth hormone prevents lactogenic differentiation of mouse mammary epithelial cells. Endocrinology 147(4):1819–1829

    Article  CAS  PubMed  Google Scholar 

  • Murtagh J, McArdle E, Gilligan E, Thornton L, Furlong F, Martin F (2004) Organization of mammary epithelial cells into 3D acinar structures requires glucocorticoid and JNK signaling. The Journal of Cell Biology 166(1):133–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Musselmann K, Kane B, Alexandrou B, Hassell JR (2006) Stimulation of collagen synthesis by insulin and proteoglycan accumulation by ascorbate in bovine keratocytes in vitro. Invest Ophthalmol Vis Sci 47(12):5260–5266

    Article  PubMed  Google Scholar 

  • Nagle JA, Ma Z, Byrne MA, White MF, Shaw LM (2004) Involvement of insulin receptor substrate 2 in mammary tumor metastasis. Mol Cell Biol 24(22):9726–9735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Najjar SM, Blakesley VA, Li Calzi S, Kato H, LeRoith D, Choice CV (1997) Differential phosphorylation of pp120 by insulin and insulin-like growth factor-1 receptors: role for the C-terminal domain of the β-subunit†. Biochemistry 36(22):6827–6834

    Article  CAS  PubMed  Google Scholar 

  • Naylor MJ, Li N, Cheung J, Lowe ET, Lambert E, Marlow R, Wang P, Schatzmann F, Wintermantel T, Schüetz G, Clarke AR, Mueller U, Hynes NE, Streuli CH (2005) Ablation of β1 integrin in mammary epithelium reveals a key role for integrin in glandular morphogenesis and differentiation. The Journal of Cell Biology 171(4):717–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neubauer SH, Ferris AM, Chase CG, Fanelli J, Thompson CA, Lammi-Keefe CJ, Clark RM, Jensen RG, Bendel RB, Green KW (1993) Delayed lactogenesis in women with insulin-dependent diabetes mellitus. The American Journal of Clinical Nutrition 58(1):54–60

    Article  CAS  PubMed  Google Scholar 

  • Neville MC, Morton J (2001) Physiology and endocrine changes underlying human lactogenesis II. The Journal of Nutrition 131(11):3005S-S3008

    Article  CAS  PubMed  Google Scholar 

  • Neville M, McFadden T, Forsyth I (2002) Hormonal regulation of mammary differentiation and milk secretion. Journal of Mammary Gland Biololgy and Neoplasia 7(1):49–66

    Article  Google Scholar 

  • Neville MC, Webb P, Ramanathan P, Mannino MP, Pecorini C, Monks J, Anderson SM, MacLean P (2013) The insulin receptor plays an important role in secretory differentiation in the mammary gland. American Journal of Endocrinology and metabolism 305(9):1103–1114

    Article  Google Scholar 

  • Nicholas KR, Topper YJ (1983) Anti-insulin receptor serum mimics the developmental role of insulin in mouse mammary explants. Biochem Biophys Res Commun 111(3):988–993

    Article  CAS  PubMed  Google Scholar 

  • Nicholas KR, Sankaran L, Topper YJ (1983) A unique and essential role for insulin in the phenotypic expression of rat mammary epithelial cells unrelated to its function in cell maintenance. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 763(3):309–314

    Article  CAS  Google Scholar 

  • Nicholas KR, Tyndale-Biscoe CH (1985) Prolactin-dependent accumulation of α-lactalbumin in mammary gland explants from the pregnant tammar wallaby (Macropus eugenii). J Endocrinol 106(3):337–342

    Article  CAS  PubMed  Google Scholar 

  • Nicholas KR, Collet C, Joseph R, Sankaran L (1991) Hormone-responsive survival of mammary gland explants from the pregnant tammar wallaby (Macropus eugenii) In the absence of exogenous hormones and growth factors. Comp Biochem Physiol A Physiol 100(1):163–167

    Article  CAS  Google Scholar 

  • Polyak K and Kalluri R (2010) The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol 2(11).

  • Oddy WH, Li J, Landsborough L, Kendall GE, Henderson S, Downie J (2006) The association of maternal overweight and obesity with breastfeeding duration. The Journal of Pediatrics 149(2):185–191

    Article  PubMed  Google Scholar 

  • Riley LG, Gardiner-Garden M, Thomson PC, Wynn PC, Williamson P, Raadsma HW, Sheehy PA (2010) The influence of extracellular matrix and prolactin on global gene expression profiles of primary bovine mammary epithelial cells in vitro. Anim Genet 41(1):55–63

    Article  CAS  PubMed  Google Scholar 

  • Riordan J and Wambach K (2010) Breastfeeding and human lactation, Jones and Bartlett Publishers.

  • Romagnolo D, and DiAugustine RP (1994) The mammary gland: protein factory of the future. Environ Health Perspect 102(8): 644-646

  • Rooney N, Streuli CH (2011) How integrins control mammary epithelial differentiation: a possible role for the ILK–PINCH–Parvin complex. FEBS Lett 585(11):1663–1672

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Torres A, Melón J, Muñoz FJ (1998) Insulin stimulates collagen synthesis in vascular smooth muscle cells from elderly patients. Gerontology 44(3):144–148

    Article  CAS  PubMed  Google Scholar 

  • Ryu RJ, Hays KE and Hebert MF (2014) Gestational diabetes mellitus management with oral hypoglycemic agents. Semin Perinatol 38(8):508-515

  • Sharp J, Cane K, Mailer S, Oosthuizen W, Arnould J, Nicholas K (2006) Species-specific cell-matrix interactions are essential for differentiation of alveoli like structures and milk gene expression in primary mammary cells of the Cape fur seal (Arctocephalus pusillus pusillus). Matrix Biol 25(7):430–442

    Article  CAS  PubMed  Google Scholar 

  • Sharp J, Mailer S, Thomson P, Lefevre C, Nicholas K (2008) Identification and transcript analysis of a novel wallaby (Macropus eugenii) basal-like breast cancer cell line. Molecular Cancer 7(1):1

    Article  PubMed  PubMed Central  Google Scholar 

  • Siddle K (2011) Signalling by insulin and IGF receptors: supporting acts and new players. J Mol Endocrinol 47(1):R1–R10

    Article  CAS  PubMed  Google Scholar 

  • Siddle K, Ursø B, Niesler CA, Cope DL, Molina L, Surinya KH, Soos MA (2001) Specificity in ligand binding and intracellular signalling by insulin and insulin-like growth factor receptors. Biochem Soc Trans 29(4):513–525

    Article  CAS  PubMed  Google Scholar 

  • Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:1-25

  • Sobolewska A, Motyl T, Gajewska M (2011) Role and regulation of autophagy in the development of acinar structures formed by bovine BME-UV1 mammary epithelial cells. Eur J Cell Biol 90(10):854–864

    Article  CAS  PubMed  Google Scholar 

  • Soule HD, Maloney TM, Wolman SR, Peterson WD, Brenz R, McGrath CM, Russo J, Pauley RJ, Jones RF, Brooks SC (1990) Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Can Res 50(18):6075–6086

    CAS  Google Scholar 

  • Stelwagen K, McFadden HA, Demmer J (1999) Prolactin, alone or in combination with glucocorticoids, enhances tight junction formation and expression of the tight junction protein occludin in mammary cells. Mol Cell Endocrinol 156(1–2):55–61

    Article  CAS  PubMed  Google Scholar 

  • Streuli C (1993) Extracellular matrix and gene expression in mammary epithelium. Semin Cell Biol 4(3):203–212

    Article  CAS  PubMed  Google Scholar 

  • Talhouk RS, Neiswander RL, Schanbacher FL (1990) In vitro culture of cryopreserved bovine mammary cells on collagen gels: Synthesis and secretion of casein and lactoferrin. Tissue Cell 22(5):583–599

    Article  CAS  PubMed  Google Scholar 

  • Topper Y, Freeman C (1980) Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev 60(4):1049–1106

    Article  CAS  PubMed  Google Scholar 

  • Trott J, Vonderhaar B, Hovey R (2008) Historical perspectives of prolactin and growth hormone as mammogens, lactogens and Galactagogues—Agog for the future! Journal of Mammary Gland Biology and Neoplasia 13(1):3–11

    Article  PubMed  Google Scholar 

  • Wanyonyi SS, Lefevre C, Sharp JA, Nicholas KR (2013) The extracellular matrix locally regulates asynchronous concurrent lactation in tammar wallaby (Macropus eugenii). Matrix Biol 32(6):342–351

    Article  CAS  PubMed  Google Scholar 

  • Werner H, Weinstein D, Bentov I (2008) Similarities and differences between insulin and IGF-I: structures, receptors, and signalling pathways. Arch Physiol Biochem 114(1):17–22

    Article  CAS  PubMed  Google Scholar 

  • Williams CM, Engler AJ, Slone RD, Galante LL, Schwarzbauer JE (2008) Fibronectin expression modulates mammary epithelial cell proliferation during acinar differentiation. Can Res 68(9):3185–3192

    Article  CAS  Google Scholar 

  • Woo PL, Cha HH, Singer KL, Firestone GL (1996) Antagonistic regulation of tight junction dynamics by glucocorticoids and transforming growth factor- in mouse mammary epithelial cells. J Biol Chem 271(1):404–412

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Phung H, Freebairn L, Sexton R, Raulli A, Kelly P (2019) Contribution of maternal overweight and obesity to the occurrence of adverse pregnancy outcomes. Aust N Z J Obstet Gynaecol 59(3):367–374

    Article  PubMed  Google Scholar 

  • Zettl KS, Sjaastad MD, Riskin PM, Parry G, Machen TE, Firestone GL (1992) Glucocorticoid-induced formation of tight junctions in mouse mammary epithelial cells in vitro. Proc Natl Acad Sci 89(19):9069–9073

    Article  CAS  PubMed  Google Scholar 

  • Zhu W and Nelson CM (2013) PI3K regulates branch initiation and extension of cultured mammary epithelia via Akt and Rac1 respectively. Developmentalbiology, 379(2):235–245.

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Institute for Frontier Materials, Deakin University, Geelong, 3216, Australia

    Ashalyn P. Watt, Cynthia S. Wong & Julie A. Sharp

  2. Division of Bioinformatics, Walter and Eliza Hall Medical Research Institute, 3000, Melbourne, Australia

    Christophe Lefevre

  3. Peter MacCallum Cancer Research Institute, East Melbourne, 3002, Australia

    Christophe Lefevre

  4. Faculty of Pharmacy and Pharmaceutical Sciences, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3052, Australia

    Kevin R. Nicholas

Authors
  1. Ashalyn P. Watt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christophe Lefevre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cynthia S. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kevin R. Nicholas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julie A. Sharp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashalyn P. Watt.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Watt, A.P., Lefevre, C., Wong, C.S. et al. Insulin regulates human mammosphere development and function. Cell Tissue Res 384, 333–352 (2021). https://doi.org/10.1007/s00441-020-03360-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-020-03360-0

Keywords

Search

Navigation