Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Mammary Gland Biology and Neoplasia
Published in: Journal of Mammary Gland Biology and Neoplasia 1/2010

01-03-2010

Gene Expression in the Third Dimension: The ECM-nucleus Connection

Authors: Virginia A. Spencer, Ren Xu, Mina J. Bissell

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 1/2010

Login to get access

Abstract

Decades ago, we and others proposed that the dynamic interplay between a cell and its surrounding environment dictates cell phenotype and tissue structure. Whereas much has been discovered about the effects of extracellular matrix molecules on cell growth and tissue-specific gene expression, the nuclear mechanisms through which these molecules promote these physiological events remain unknown. Using mammary epithelial cells as a model, the purpose of this review is to discuss how the extracellular matrix influences nuclear structure and function in a three-dimensional context to promote epithelial morphogenesis and function in the mammary gland.
Literature
1.
Getzenberg RH, Pienta KJ, Ward WS, Coffey DS. Nuclear structure and the three-dimensional organization of DNA. J Cell Biochem. 1991;47(4):289–99.CrossRefPubMed
2.
Hager GL, Nagaich AK, Johnson TA, Walker DA, John S. Dynamics of nuclear receptor movement and transcription. Biochim Biophys Acta. 2004;1677(1–3):46–51.PubMed
3.
4.
Cremer T, Cremer M, Dietzel S, Muller S, Solovei I, Fakan S. Chromosome territories-a functional nuclear landscape. Curr Opin Cell Biol. 2006;18(3):307–16.CrossRefPubMed
5.
Mahy NL, Perry PE, Bickmore WA. Gene density and transcription influence the localization of chromatin outside of chromosome territories detectable by FISH. J Cell Biol. 2002;159(5):753–63.CrossRefPubMed
6.
Scheuermann MO, Tajbakhsh J, Kurz A, Saracoglu K, Eils R, Lichter P. Topology of genes and nontranscribed sequences in human interphase nuclei. Exp Cell Res. 2004;301(2):266–79.CrossRefPubMed
7.
Tajbakhsh J, Luz H, Bornfleth H, Lampel S, Cremer C, Lichter P. Spatial distribution of GC- and AT-rich DNA sequences within human chromosome territories. Exp Cell Res. 2000;255(2):229–37.CrossRefPubMed
8.
Nickerson J. Experimental observations of a nuclear matrix. J Cell Sci. 2001;114(Pt 3):463–74.PubMed
9.
Zaidi SK, Young DW, Javed A, Pratap J, Montecino M, van Wijnen A, et al. Nuclear microenvironments in biological control and cancer. Nat Rev Cancer. 2007;7(6):454–63.CrossRefPubMed
10.
11.
Lamond AI, Spector DL. Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol. 2003;4(8):605–12.CrossRefPubMed
12.
13.
Efroni S, Duttagupta R, Cheng J, Dehghani H, Hoeppner DJ, Dash C, et al. Global transcription in pluripotent embryonic stem cells. Cell Stem Cell. 2008;2(5):437–47.CrossRefPubMed
14.
Lee JH, Hart SR, Skalnik DG. Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis. 2004;38(1):32–8.CrossRefPubMed
15.
Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell. 2006;10(1):105–16.CrossRefPubMed
16.
Hager GL, Elbi C, Becker M. Protein dynamics in the nuclear compartment. Curr Opin Genet Dev. 2002;12(2):137–41.CrossRefPubMed
17.
Bissell MJ, Hall HG, Parry G. How does the extracellular matrix direct gene expression? J Theor Biol. 1982;99(1):31–68.CrossRefPubMed
18.
Ferguson JE, Schor AM, Howell A, Ferguson MW. Changes in the extracellular matrix of the normal human breast during the menstrual cycle. Cell Tissue Res. 1992;268(1):167–77.CrossRefPubMed
19.
Keely PJ, Wu JE, Santoro SA. The spatial and temporal expression of the alpha 2 beta 1 integrin and its ligands, collagen I, collagen IV, and laminin, suggest important roles in mouse mammary morphogenesis. Differentiation. 1995;59(1):1–13.CrossRefPubMed
20.
Stoeckelhuber M, Stumpf P, Hoefter EA, Welsch U. Proteoglycan-collagen associations in the non-lactating human breast connective tissue during the menstrual cycle. Histochem Cell Biol. 2002;118(3):221–30.PubMed
21.
Woodward TL, Mienaltowski AS, Modi RR, Bennett JM, Haslam SZ. Fibronectin and the alpha(5)beta(1) integrin are under developmental and ovarian steroid regulation in the normal mouse mammary gland. Endocrinology. 2001;142(7):3214–22.CrossRefPubMed
22.
Russo J, Russo IH. DNA labeling index and structure of the rat mammary gland as determinants of its susceptibility to carcinogenesis. J Natl Cancer Inst. 1978;61(6):1451–9.PubMed
23.
Williams JM, Daniel CW. Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol. 1983;97(2):274–90.CrossRefPubMed
24.
Klinowska TC, Soriano JV, Edwards GM, Oliver JM, Valentijn AJ, Montesano R, et al. Laminin and beta1 integrins are crucial for normal mammary gland development in the mouse. Dev Biol. 1999;215(1):13–32.CrossRefPubMed
25.
Prince JM, Klinowska TC, Marshman E, Lowe ET, Mayer U, Miner J, et al. Cell-matrix interactions during development and apoptosis of the mouse mammary gland in vivo. Dev Dyn. 2002;223(4):497–516.CrossRefPubMed
26.
Ghajar CM, Bissell MJ. Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging. Histochem Cell Biol. 2008;130(6):1105–18.CrossRefPubMed
27.
Michalopoulos G. Pitot HC. Primary culture of parenchymal liver cells on collagen membranes Morphological and biochemical observations Exp Cell Res. 1975;94(1):70–8.
28.
Emerman JT, Burwen SJ, Pitelka DR. Substrate properties influencing ultrastructural differentiation of mammary epithelial cells in culture. Tissue Cell. 1979;11(1):109–19.CrossRefPubMed
29.
Emerman JT, Pitelka DR. Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes. In Vitro. 1977;13(5):316–28.CrossRefPubMed
30.
Lee EY, Lee WH, Kaetzel CS, Parry G, Bissell MJ. Interaction of mouse mammary epithelial cells with collagen substrata: regulation of casein gene expression and secretion. Proc Natl Acad Sci U S A. 1985;82(5):1419–23.CrossRefPubMed
31.
Lee EY, Parry G, Bissell MJ. Modulation of secreted proteins of mouse mammary epithelial cells by the collagenous substrata. J Cell Biol. 1984;98(1):146–55.CrossRefPubMed
32.
Streuli CH, Bissell MJ. Expression of extracellular matrix components is regulated by substratum. J Cell Biol. 1990;110(4):1405–15.CrossRefPubMed
33.
Streuli CH, Schmidhauser C, Bailey N, Yurchenco P, Skubitz AP, Roskelley C, et al. Laminin mediates tissue-specific gene expression in mammary epithelia. J Cell Biol. 1995;129(3):591–603.CrossRefPubMed
34.
Roskelley CD, Desprez PY, Bissell MJ. Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction. Proc Natl Acad Sci U S A. 1994;91(26):12378–82.CrossRefPubMed
35.
Muschler J, Lochter A, Roskelley CD, Yurchenco P, Bissell MJ. Division of labor among the alpha6beta4 integrin, beta1 integrins, and an E3 laminin receptor to signal morphogenesis and beta-casein expression in mammary epithelial cells. Mol Biol Cell. 1999;10(9):2817–28.PubMed
36.
Weir ML, Oppizzi ML, Henry MD, Onishi A, Campbell KP, Bissell MJ, et al. Dystroglycan loss disrupts polarity and beta-casein induction in mammary epithelial cells by perturbing laminin anchoring. J Cell Sci. 2006;119(Pt 19):4047–58.CrossRefPubMed
37.
Henry MD, Campbell KP. A role for dystroglycan in basement membrane assembly. Cell. 1998;95(6):859–70.CrossRefPubMed
38.
Akhtar N, Marlow R, Lambert E, Schatzmann F, Lowe ET, Cheung J, et al. Molecular dissection of integrin signalling proteins in the control of mammary epithelial development and differentiation. Development. 2009;136(6):1019–27.CrossRefPubMed
39.
Myers CA, Schmidhauser C, Mellentin-Michelotti J, Fragoso G, Roskelley CD, Casperson G, et al. Characterization of BCE-1, a transcriptional enhancer regulated by prolactin and extracellular matrix and modulated by the state of histone acetylation. Mol Cell Biol. 1998;18(4):2184–95.PubMed
40.
Wakao H, Gouilleux F, Groner B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J. 1994;13(9):2182–91.PubMed
41.
Xu R, Nelson CM, Muschler JL, Veiseh M, Vonderhaar BK, Bissell MJ. Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specific function. J Cell Biol. 2009;184(1):57–66.CrossRefPubMed
42.
Sheetz MP. Cell control by membrane-cytoskeleton adhesion. Nat Rev Mol Cell Biol. 2001;2(5):392–6.CrossRefPubMed
43.
Wiesner S, Legate KR, Fassler R. Integrin-actin interactions. Cell Mol Life Sci. 2005;62(10):1081–99.CrossRefPubMed
44.
Fridkin A, Penkner A, Jantsch V, Gruenbaum Y. SUN-domain and KASH-domain proteins during development, meiosis and disease. Cell Mol Life Sci. 2009;66(9):1518–33.CrossRefPubMed
45.
Starr DA, Fischer JA. KASH ’n Karry: the KASH domain family of cargo-specific cytoskeletal adaptor proteins. Bioessays. 2005;27(11):1136–46.CrossRefPubMed
46.
Tzur YB, Wilson KL, Gruenbaum Y. SUN-domain proteins: ‘Velcro’ that links the nucleoskeleton to the cytoskeleton. Nat Rev Mol Cell Biol. 2006;7(10):782–8.CrossRefPubMed
47.
Dahl KN, Ribeiro AJ, Lammerding J. Nuclear shape, mechanics, and mechanotransduction. Circ Res. 2008;102(11):1307–18.CrossRefPubMed
48.
Maniotis AJ, Chen CS, Ingber DE. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci U S A. 1997;94(3):849–54.CrossRefPubMed
49.
Lammerding J, Schulze PC, Takahashi T, Kozlov S, Sullivan T, Kamm RD, et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest. 2004;113(3):370–8.PubMed
50.
Weaver VM, Petersen OW, Wang F, Larabell CA, Briand P, Damsky C, et al. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol. 1997;137(1):231–45.CrossRefPubMed
51.
Zoubiane GS, Valentijn A, Lowe ET, Akhtar N, Bagley S, Gilmore AP, et al. A role for the cytoskeleton in prolactin-dependent mammary epithelial cell differentiation. J Cell Sci. 2004;117(Pt 2):271–80.CrossRefPubMed
52.
Alcaraz J, Xu R, Mori H, Nelson CM, Mroue R, Spencer VA, et al. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia. EMBO J. 2008;27(21):2829–38.CrossRefPubMed
53.
Spencer VA, Xu R, Bissell MJ. Extracellular matrix, nuclear and chromatin structure, and gene expression in normal tissues and malignant tumors: a work in progress. Adv Cancer Res. 2007;97:275–94.CrossRefPubMed
54.
Fournier MV, Martin KJ, Kenny PA, Xhaja K, Bosch I, Yaswen P, et al. Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer. Cancer Res. 2006;66(14):7095–102.CrossRefPubMed
55.
Petersen OW, Ronnov-Jessen L, Howlett AR, Bissell MJ. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci U S A. 1992;89(19):9064–8.CrossRefPubMed
56.
Le Beyec J, Xu R, Lee SY, Nelson CM, Rizki A, Alcaraz J, et al. Cell shape regulates global histone acetylation in human mammary epithelial cells. Exp Cell Res. 2007;313(14):3066–75.CrossRefPubMed
57.
Maniotis AJ, Valyi-Nagy K, Karavitis J, Moses J, Boddipali V, Wang Y, et al. Chromatin organization measured by AluI restriction enzyme changes with malignancy and is regulated by the extracellular matrix and the cytoskeleton. Am J Pathol. 2005;166(4):1187–203.PubMed
58.
Plachot C, Lelievre SA. DNA methylation control of tissue polarity and cellular differentiation in the mammary epithelium. Exp Cell Res. 2004;298(1):122–32.CrossRefPubMed
59.
Kaminker P, Plachot C, Kim SH, Chung P, Crippen D, Petersen OW, et al. Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2. J Cell Sci. 2005;118(Pt 6):1321–30.CrossRefPubMed
60.
Knowles DW, Sudar D, Bator-Kelly C, Bissell MJ, Lelievre SA. Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype. Proc Natl Acad Sci U S A. 2006;103(12):4445–50.CrossRefPubMed
61.
Lelievre SA, Weaver VM, Nickerson JA, Larabell CA, Bhaumik A, Petersen OW, et al. Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus. Proc Natl Acad Sci U S A. 1998;95(25):14711–6.CrossRefPubMed
62.
Boisvert FM, Hendzel MJ, Bazett-Jones DP. Promyelocytic leukemia (PML) nuclear bodies are protein structures that do not accumulate RNA. J Cell Biol. 2000;148(2):283–92.CrossRefPubMed
63.
Negorev D, Maul GG. Cellular proteins localized at and interacting within ND10/PML nuclear bodies/PODs suggest functions of a nuclear depot. Oncogene. 2001;20(49):7234–42.CrossRefPubMed
64.
Torok D, Ching RW, Bazett-Jones DP. PML nuclear bodies as sites of epigenetic regulation. Front Biosci. 2009;14:1325–36.CrossRefPubMed
65.
Shen TH, Lin HK, Scaglioni PP, Yung TM, Pandolfi PP. The mechanisms of PML-nuclear body formation. Mol Cell. 2006;24(3):331–9.CrossRefPubMed
66.
Lin DY, Huang YS, Jeng JC, Kuo HY, Chang CC, Chao TT, et al. Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell. 2006;24(3):341–54.CrossRefPubMed
67.
Takahashi H, Hatakeyama S, Saitoh H, Nakayama KI. Noncovalent SUMO-1 binding activity of thymine DNA glycosylase (TDG) is required for its SUMO-1 modification and colocalization with the promyelocytic leukemia protein. J Biol Chem. 2005;280(7):5611–21.CrossRefPubMed
68.
69.
Bissell MJ, Weaver VM, Lelievre SA, Wang F, Petersen OW, Schmeichel KL. Tissue structure, nuclear organization, and gene expression in normal and malignant breast. Cancer Res. 1999;59(7 Suppl):1757s–64s. discussion 1763s–4s.
70.
Lin CQ, Bissell MJ. Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 1993;7(9):737–43.PubMed
71.
Roskelley CD, Srebrow A, Bissell MJ. A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression. Curr Opin Cell Biol. 1995;7(5):736–47.CrossRefPubMed
72.
Butcher DT, Alliston T, Weaver VM. A tense situation: forcing tumour progression. Nat Rev Cancer. 2009;9(2):108–22.CrossRefPubMed
73.
Close MJ, Howlett AR, Roskelley CD, Desprez PY, Bailey N, Rowning B, et al. Lactoferrin expression in mammary epithelial cells is mediated by changes in cell shape and actin cytoskeleton. J Cell Sci. 1997;110(Pt 22):2861–71.PubMed
74.
Gouilleux F, Wakao H, Mundt M, Groner B. Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. Embo J. 1994;13(18):4361–9.PubMed
75.
Xu R, Spencer VA, Bissell MJ. Extracellular matrix-regulated gene expression requires cooperation of SWI/SNF and transcription factors. J Biol Chem. 2007;282(20):14992–9.CrossRefPubMed
Metadata
Title
Gene Expression in the Third Dimension: The ECM-nucleus Connection
Authors
Virginia A. Spencer
Ren Xu
Mina J. Bissell
Publication date
01-03-2010
Publisher
Springer US
Published in
Journal of Mammary Gland Biology and Neoplasia / Issue 1/2010
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-010-9163-3

Other articles of this Issue 1/2010

Journal of Mammary Gland Biology and Neoplasia 1/2010 Go to the issue

OriginalPaper

The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

Preface

Epigenetics in Mammary Gland Biology and Cancer

OriginalPaper

Tissue Polarity-Dependent Control of Mammary Epithelial Homeostasis and Cancer Development: an Epigenetic Perspective

OriginalPaper

Breast Cancer Epigenetics: From DNA Methylation to microRNAs

OriginalPaper

Epigenetic Modifications in 3D: Nuclear Organization of the Differentiating Mammary Epithelial Cell

OriginalPaper

Epigenetic Regulation in Estrogen Receptor Positive Breast Cancer—Role in Treatment Response
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits