Skip to main content
Erschienen in: Breast Cancer Research 2/2006

01.04.2006 | Review

Key stages in mammary gland development - Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ

verfasst von: Christine J Watson

Erschienen in: Breast Cancer Research | Ausgabe 2/2006

Einloggen, um Zugang zu erhalten

Abstract

Involution of the mammary gland is an essential process that removes the milk-producing epithelial cells when they become redundant at weaning. It is a two-step process that involves the death of the secretory epithelium and its replacement by adipo-cytes. During the first phase, remodelling is inhibited and apoptotic cells can be seen in the lumena of the alveoli. In the second phase, apoptosis is accompanied by remodelling of the surrounding stroma and re-differentiation of the adipocytes. Considerable effort has been directed towards understanding the molecular mechanisms of the involution process and this has resulted in the identification of the principal signalling pathways involved.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Gräper L: Arch Zellforsch. 1914, 12: 373-394. Gräper L: Arch Zellforsch. 1914, 12: 373-394.
2.
Zurück zum Zitat Kerr J, Wyllie A, Currie A: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972, 26: 239-257.CrossRefPubMedPubMedCentral Kerr J, Wyllie A, Currie A: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972, 26: 239-257.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Danial NN, Korsmeyer SJ: Cell death: Critical control points. Cell. 2004, 116: 205-219. 10.1016/S0092-8674(04)00046-7.CrossRefPubMed Danial NN, Korsmeyer SJ: Cell death: Critical control points. Cell. 2004, 116: 205-219. 10.1016/S0092-8674(04)00046-7.CrossRefPubMed
4.
Zurück zum Zitat Melino G, Knight RA, Nicotera P: How many ways to die? How many different models of cell death?. Cell Death Diff. 2005, 12: 1457-1462. 10.1038/sj.cdd.4401781.CrossRef Melino G, Knight RA, Nicotera P: How many ways to die? How many different models of cell death?. Cell Death Diff. 2005, 12: 1457-1462. 10.1038/sj.cdd.4401781.CrossRef
5.
Zurück zum Zitat Lund LR, Romer J, Thomasset N, Solberg H, Pyke C, Bissell MJ, Danø K, Werb Z: Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependant pathways. Development. 1996, 122: 181-193.PubMedPubMedCentral Lund LR, Romer J, Thomasset N, Solberg H, Pyke C, Bissell MJ, Danø K, Werb Z: Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependant pathways. Development. 1996, 122: 181-193.PubMedPubMedCentral
6.
Zurück zum Zitat Marti A, Feng Z, Altermatt HJ, Jaggi R: Milk accumulation triggers apoptosis of mammary epithelial cells. Eur J Cell Biol. 1997, 73: 158-165.PubMed Marti A, Feng Z, Altermatt HJ, Jaggi R: Milk accumulation triggers apoptosis of mammary epithelial cells. Eur J Cell Biol. 1997, 73: 158-165.PubMed
7.
Zurück zum Zitat Li M, Liu X, Robinson G, Bar-Peled U, Wagner KU, Young WS, Hennighausen L, Furth PA: Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc Natl Acad Sci USA. 1997, 94: 3425-3430. 10.1073/pnas.94.7.3425.CrossRefPubMedPubMedCentral Li M, Liu X, Robinson G, Bar-Peled U, Wagner KU, Young WS, Hennighausen L, Furth PA: Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc Natl Acad Sci USA. 1997, 94: 3425-3430. 10.1073/pnas.94.7.3425.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Feng Z, Marti A, Jehn B, Altermatt HJ, Chicaiza G, Jaggi R: Glu-cocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland. J Cell Biol. 131: 1095-1103. 10.1083/jcb.131.4.1095. Feng Z, Marti A, Jehn B, Altermatt HJ, Chicaiza G, Jaggi R: Glu-cocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland. J Cell Biol. 131: 1095-1103. 10.1083/jcb.131.4.1095.
9.
Zurück zum Zitat Zettl KS, Sjaastad MD, Riskin PM, Parry G, Machen TE, Firestone GL: Glucocorticoid-induced formation of tight junctions in mouse mammary epithelial cells in vitro. Proc Natl Acad Sci USA. 1992, 89: 9069-9073. 10.1073/pnas.89.19.9069.CrossRefPubMedPubMedCentral Zettl KS, Sjaastad MD, Riskin PM, Parry G, Machen TE, Firestone GL: Glucocorticoid-induced formation of tight junctions in mouse mammary epithelial cells in vitro. Proc Natl Acad Sci USA. 1992, 89: 9069-9073. 10.1073/pnas.89.19.9069.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Green KA, Lund LR: ECM degrading proteases and tissue remodelling in the mammary gland. Bioessays. 2005, 27: 894-903. 10.1002/bies.20281.CrossRefPubMed Green KA, Lund LR: ECM degrading proteases and tissue remodelling in the mammary gland. Bioessays. 2005, 27: 894-903. 10.1002/bies.20281.CrossRefPubMed
11.
Zurück zum Zitat Green KA, Streuli CH: Apoptosis regulation in the mammary gland. Cell Mol Life Sci. 2004, 61: 1867-1883. 10.1007/s00018-004-3366-y.CrossRefPubMed Green KA, Streuli CH: Apoptosis regulation in the mammary gland. Cell Mol Life Sci. 2004, 61: 1867-1883. 10.1007/s00018-004-3366-y.CrossRefPubMed
12.
Zurück zum Zitat Walton KD, Wagner KU, Rucker EB, Shillingford JM, Miyoshi K, Hennighausen L: Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation. Mech Dev. 2001, 109: 281-293. 10.1016/S0925-4773(01)00549-4.CrossRefPubMed Walton KD, Wagner KU, Rucker EB, Shillingford JM, Miyoshi K, Hennighausen L: Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation. Mech Dev. 2001, 109: 281-293. 10.1016/S0925-4773(01)00549-4.CrossRefPubMed
13.
Zurück zum Zitat Schorr K, Li M, Bar-Peled U, Lewis A, Heredia A, Lewis B, Knudson CM, Korsmeyer SJ, Jäger R, Weiher H, Furth PA: Gain of Bcl-2 is more potent than bax loss in regulating mammary epithelial cell survival in vivo. Cancer Res. 1999, 59: 2541-2545.PubMed Schorr K, Li M, Bar-Peled U, Lewis A, Heredia A, Lewis B, Knudson CM, Korsmeyer SJ, Jäger R, Weiher H, Furth PA: Gain of Bcl-2 is more potent than bax loss in regulating mammary epithelial cell survival in vivo. Cancer Res. 1999, 59: 2541-2545.PubMed
14.
Zurück zum Zitat Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN: Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998, 93: 841-850. 10.1016/S0092-8674(00)81444-0.CrossRefPubMed Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN: Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998, 93: 841-850. 10.1016/S0092-8674(00)81444-0.CrossRefPubMed
15.
Zurück zum Zitat Chapman RS, Lourenco PC, Tonner E, Flint DJ, Selbert S, Takeda K, Akira S, Clarke AR, Watson CJ: Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev. 1999, 13: 2604-2616. 10.1101/gad.13.19.2604.CrossRefPubMedPubMedCentral Chapman RS, Lourenco PC, Tonner E, Flint DJ, Selbert S, Takeda K, Akira S, Clarke AR, Watson CJ: Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev. 1999, 13: 2604-2616. 10.1101/gad.13.19.2604.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Humphreys RC, Bierie B, Zhao L, Raz R, Levy D, Hennighausen L: Deletion of Stat3 blocks mammary gland involution and extends functional competence of the secretory epithelium in the absence of lactogenic stimuli. Endocrinology. 2002, 143: 3641-3650. 10.1210/en.2002-220224.CrossRefPubMed Humphreys RC, Bierie B, Zhao L, Raz R, Levy D, Hennighausen L: Deletion of Stat3 blocks mammary gland involution and extends functional competence of the secretory epithelium in the absence of lactogenic stimuli. Endocrinology. 2002, 143: 3641-3650. 10.1210/en.2002-220224.CrossRefPubMed
17.
Zurück zum Zitat Kritikou EA, Sharkey A, Abell K, Came PJ, Anderson E, Clarkson RWE, Watson CJ: A dual, non-redundant, role for LIF as a regulator of development and Stat3-mediated cell death in mammary gland. Development. 2003, 130: 3459-3468. 10.1242/dev.00578.CrossRefPubMed Kritikou EA, Sharkey A, Abell K, Came PJ, Anderson E, Clarkson RWE, Watson CJ: A dual, non-redundant, role for LIF as a regulator of development and Stat3-mediated cell death in mammary gland. Development. 2003, 130: 3459-3468. 10.1242/dev.00578.CrossRefPubMed
18.
Zurück zum Zitat Schere-Levy C, Buggiano V, Quaglino A, Gattelli A, Cirio MC, Piazzon I, Vanzulli S, Kordon EC: Leukemia inhibitory factor induces apoptosis of the mammary epithelial cells and participates in mouse mammary gland involution. Exp Cell Res. 2003, 282: 35-47. 10.1006/excr.2002.5666.CrossRefPubMed Schere-Levy C, Buggiano V, Quaglino A, Gattelli A, Cirio MC, Piazzon I, Vanzulli S, Kordon EC: Leukemia inhibitory factor induces apoptosis of the mammary epithelial cells and participates in mouse mammary gland involution. Exp Cell Res. 2003, 282: 35-47. 10.1006/excr.2002.5666.CrossRefPubMed
19.
Zurück zum Zitat Clarkson RWE, Boland MP, Kritikou EA, Lee JM, Freeman TC, Tiffen PG, Watson CJ: The genes induced by Stat3 and Stat5 in mammary epithelial cells define the roles of these Stats in mammary gland development. Mol Endo. 2006, 20: 675-685. 10.1210/me.2005-0392.CrossRef Clarkson RWE, Boland MP, Kritikou EA, Lee JM, Freeman TC, Tiffen PG, Watson CJ: The genes induced by Stat3 and Stat5 in mammary epithelial cells define the roles of these Stats in mammary gland development. Mol Endo. 2006, 20: 675-685. 10.1210/me.2005-0392.CrossRef
20.
Zurück zum Zitat Tonner E, Barber MC, Allan GJ, Beattie J, Webster J, Whitelaw CB, Flint DJ: Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice. Development. 2002, 129: 4547-4557.PubMed Tonner E, Barber MC, Allan GJ, Beattie J, Webster J, Whitelaw CB, Flint DJ: Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice. Development. 2002, 129: 4547-4557.PubMed
21.
Zurück zum Zitat Thangaraju M, Rudelius M, Bierie B, Raffeld M, Sharan S, Hen-nighausen L, Huang AM, Sterneck E: C/EBPδ is a crucial regulator of pro-apoptotic gene expression during mammary gland involution. Development. 2005, 132: 4675-4685. 10.1242/dev.02050.CrossRefPubMed Thangaraju M, Rudelius M, Bierie B, Raffeld M, Sharan S, Hen-nighausen L, Huang AM, Sterneck E: C/EBPδ is a crucial regulator of pro-apoptotic gene expression during mammary gland involution. Development. 2005, 132: 4675-4685. 10.1242/dev.02050.CrossRefPubMed
22.
Zurück zum Zitat Schwertfeger KL, Richert MM, Anderson SM: Mammary gland involution is delayed by activated Akt in transgenic mice. Mol Endo. 2001, 15: 867-881. 10.1210/me.15.6.867.CrossRef Schwertfeger KL, Richert MM, Anderson SM: Mammary gland involution is delayed by activated Akt in transgenic mice. Mol Endo. 2001, 15: 867-881. 10.1210/me.15.6.867.CrossRef
23.
Zurück zum Zitat Abell K, Bilancio A, Clarkson RW, Tiffen PG, Altaparmakov AI, Burdon TG, Asano T, Vanhaesebroeck B, Watson CJ: Stat3-induced apoptosis requires a molecular switch in PI(3)K subunit composition. Nat Cell Biol. 2005, 7: 392-398. 10.1038/ncb1242.CrossRefPubMed Abell K, Bilancio A, Clarkson RW, Tiffen PG, Altaparmakov AI, Burdon TG, Asano T, Vanhaesebroeck B, Watson CJ: Stat3-induced apoptosis requires a molecular switch in PI(3)K subunit composition. Nat Cell Biol. 2005, 7: 392-398. 10.1038/ncb1242.CrossRefPubMed
24.
Zurück zum Zitat Clarkson RW, Wayland MT, Lee J, Freeman T, Watson CJ: Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression. Breast Cancer Res. 2004, 6: R92-109. 10.1186/bcr754.CrossRefPubMed Clarkson RW, Wayland MT, Lee J, Freeman T, Watson CJ: Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression. Breast Cancer Res. 2004, 6: R92-109. 10.1186/bcr754.CrossRefPubMed
25.
Zurück zum Zitat Stein T, Morris JS, Davies CR, Weber-Hall SJ, Duffy MA, Heath VJ, Bell AK, Ferrier RK, Sandilands GP, Gusterson BA: Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3. Breast Cancer Res. 2004, 6: R75-R91. 10.1186/bcr753.CrossRefPubMed Stein T, Morris JS, Davies CR, Weber-Hall SJ, Duffy MA, Heath VJ, Bell AK, Ferrier RK, Sandilands GP, Gusterson BA: Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3. Breast Cancer Res. 2004, 6: R75-R91. 10.1186/bcr753.CrossRefPubMed
26.
Zurück zum Zitat Nguyen AV, Pollard J: Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution. Development. 2000, 127: 3107-3118.PubMed Nguyen AV, Pollard J: Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution. Development. 2000, 127: 3107-3118.PubMed
27.
Zurück zum Zitat Pullan S, Wilson J, Metcalfe A, Edwards GM, Goberdhan N, Tilly J, Hickman JA, Dive C, Streuli CH: Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium. 1996, 109: 631-642. Pullan S, Wilson J, Metcalfe A, Edwards GM, Goberdhan N, Tilly J, Hickman JA, Dive C, Streuli CH: Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium. 1996, 109: 631-642.
28.
Zurück zum Zitat Fata JE, Leco KJ, Voura EB, Yu HY, Waterhouse P, Murphy G, Moorehead RA, Khokha R: Accelerated apoptosis in the Timp-3-deficient mammary gland. J Clin Invest. 2001, 108: 831-841. 10.1172/JCI200113171.CrossRefPubMedPubMedCentral Fata JE, Leco KJ, Voura EB, Yu HY, Waterhouse P, Murphy G, Moorehead RA, Khokha R: Accelerated apoptosis in the Timp-3-deficient mammary gland. J Clin Invest. 2001, 108: 831-841. 10.1172/JCI200113171.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Alexander CM, Selvarajan S, Mudgett J, Werb Z: Stromelysin-1 regulates adipogenesis during mammary gland involution. J Cell Biol. 2001, 152: 693-703. 10.1083/jcb.152.4.693.CrossRefPubMedPubMedCentral Alexander CM, Selvarajan S, Mudgett J, Werb Z: Stromelysin-1 regulates adipogenesis during mammary gland involution. J Cell Biol. 2001, 152: 693-703. 10.1083/jcb.152.4.693.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Lund LR, Bjorn SF, Sternlicht MD, Nielsen BS, Solberg H, Usher PA, Osterby R, Christensen IJ, Stephens RW, Bugge TH, et al: Lactational competence and involution of the mouse mammary gland require plasminogen. Development. 2000, 127: 4481-4492.PubMed Lund LR, Bjorn SF, Sternlicht MD, Nielsen BS, Solberg H, Usher PA, Osterby R, Christensen IJ, Stephens RW, Bugge TH, et al: Lactational competence and involution of the mouse mammary gland require plasminogen. Development. 2000, 127: 4481-4492.PubMed
31.
Zurück zum Zitat Selvarajan S, Lund LR, Takeuchi T, Craik CS, Werb Z: A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation. 2001, 3: 267-275. Selvarajan S, Lund LR, Takeuchi T, Craik CS, Werb Z: A plasma kallikrein-dependent plasminogen cascade required for adipocyte differentiation. 2001, 3: 267-275.
32.
Zurück zum Zitat Monks J, Rosner D, Geske FJ, Lehman L, Hanson L, Neville MC, Fadok VA: Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ. 2005, 12: 107-114. 10.1038/sj.cdd.4401517.CrossRefPubMed Monks J, Rosner D, Geske FJ, Lehman L, Hanson L, Neville MC, Fadok VA: Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ. 2005, 12: 107-114. 10.1038/sj.cdd.4401517.CrossRefPubMed
33.
Zurück zum Zitat Hanayama R, Nagata S: Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8. Proc Natl Acad Sci U S A. 2005, 102: 16886-16891. 10.1073/pnas.0508599102.CrossRefPubMedPubMedCentral Hanayama R, Nagata S: Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8. Proc Natl Acad Sci U S A. 2005, 102: 16886-16891. 10.1073/pnas.0508599102.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Marti A, Ritter PM, Jager R, Lazar H, Baltzer A, Schenkel J, Declercq W, Vandenabeele P, Jaggi R: Mouse mammary gland involution is associated with cytochrome c release and caspase activation. Mech Dev. 104: 89-98. 10.1016/S0925-4773(01)00381-1. Marti A, Ritter PM, Jager R, Lazar H, Baltzer A, Schenkel J, Declercq W, Vandenabeele P, Jaggi R: Mouse mammary gland involution is associated with cytochrome c release and caspase activation. Mech Dev. 104: 89-98. 10.1016/S0925-4773(01)00381-1.
Metadaten
Titel
Key stages in mammary gland development - Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ
verfasst von
Christine J Watson
Publikationsdatum
01.04.2006
Verlag
BioMed Central
Erschienen in
Breast Cancer Research / Ausgabe 2/2006
Elektronische ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1401

Weitere Artikel der Ausgabe 2/2006

Breast Cancer Research 2/2006 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.