Top

Journal of Mammary Gland Biology and Neoplasia

Published in:

01-03-2010

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

Author: Sophie A. Lelièvre

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

Abstract

The basoapical organization of monolayered epithelia is defined by the presence of hemidesmosomes at the basal cellular pole, where the cell makes contacts with the basement membrane, and tight junctions at the opposite apical pole. In the mammary gland, tight junctions seal cell–cell contacts against the lumen and separate the apical and basolateral cell membranes. This separation is critical to organize intracellular signaling pathways and the cytoskeleton. The study of the impact of the highly organized apical pole, and notably apical polarity regulators (Crb complex, Par complex, and Scrib, Dlg, Lgl proteins) and tight junction proteins on cell phenotype and gene expression has revealed an intricate relationship between apical polarity and the cell nucleus. The goal of this review is to highlight the role of the apical pole of the tissue polarity axis in the epigenetic control of tissue phenotype. The organization of the apical pole and its importance in mammary homeostasis and tumorigenesis will be emphasized before presenting how apical polarity proteins impact gene expression indirectly, by influencing signal transduction and the location of transcription regulators, and directly, by participating in chromatin-associated complexes. The relationship between apical polarity and cell nucleus organizations might explain how apical polarity proteins could switch from nuclear repressors to nuclear promoters of cancerous behavior following alterations in the apical pole. The impact of apical polarity proteins on epigenetic mechanisms of gene expression will be discussed in light of increased evidence supporting a role for apical polarity in the fate of breast neoplasms.

Morange M. The relations between genetics and epigenetics: a historical point of view. Ann N Y Acad Sci. 2002;981:50–60.PubMedCrossRef

Lelievre SA, Bissell MJ. Communication between the cell membrane and the nucleus: role of protein compartmentalization. J Cell Biochem Suppl. 1998;30–31:250–63.PubMed

Lelièvre SA. Contributions of extracellular matrix signaling and tissue architecture to nuclear mechanisms and spatial organization of gene expression control. Biochim Biophys Acta. 2009;1790(9):925–35.PubMed

Farquhar MG, Palade GE. Junctional complexes in various epithelia. J Cell Biol. 1963;17:375–412.PubMed

Matter K, Balda MS. Epithelial tight junctions, gene expression and nucleo-junctional interplay. J Cell Sci. 2007;120(Pt 9):1505–11.PubMed

Shennan DB, Peaker M. Transport of milk constituents by the mammary gland. Physiol Rev. 2000;80(3):925–51.PubMed

Blaug S, Rymer J, Jalickee S, Miller SS. P2 purinoceptors regulate calcium-activated chloride and fluid transport in 31EG4 mammary epithelia. Am J Physiol Cell Physiol. 2003;284(4):C897–909.PubMed

Fanning AS, Anderson JM. Zonula occludens-1 and -2 are cytosolic scaffolds that regulate the assembly of cellular junctions. Ann N Y Acad Sci. 2009;1165:113–20.PubMed

Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol. 2001;2(4):285–93.PubMed

10.

Schneeberger EE, Lynch RD. The tight junction: a multifunctional complex. Am J Physiol Cell Physiol. 2004;286(6):C1213–28.PubMed

11.

Nguyen DA, Neville MC. Tight junction regulation in the mammary gland. J Mammary Gland Biol Neoplasia. 1998;3(3):233–46.PubMed

12.

Blanchard AA, Watson PH, Shiu RP, Leygue E, Nistor A, Wong P, et al. Differential expression of claudin 1, 3, and 4 during normal mammary gland development in the mouse. DNA Cell Biol. 2006;25(2):79–86.PubMed

13.

Ivanov AI, Hunt D, Utech M, Nusrat A, Parkos CA. Differential roles for actin polymerization and a myosin II motor in assembly of the epithelial apical junctional complex. Mol Biol Cell. 2005;16(6):2636–50.PubMed

14.

Miyoshi J, Takai Y. Structural and functional associations of apical junctions with cytoskeleton. Biochim Biophys Acta. 2008;1778(3):670–91.PubMed

15.

Hartsock A, Nelson WJ. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta. 2008;1778(3):660–9.PubMed

16.

Gonzalez-Mariscal L, Tapia R, Chamorro D. Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta. 2008;1778(3):729–56.PubMed

17.

Islas S, Vega J, Ponce L, Gonzalez-Mariscal L. Nuclear localization of the tight junction protein ZO-2 in epithelial cells. Exp Cell Res. 2002;274(1):138–48.PubMed

18.

Paris L, Tonutti L, Vannini C, Bazzoni G. Structural organization of the tight junctions. Biochim Biophys Acta. 2008;1778(3):646–59.PubMed

19.

Abad PC, Yagci B, Lelièvre SA. Nanoprocesses in gene expression. In: Nalwa HS, editor. Encyclopedia of Nanoscience and Nanotechnology, Vols 11–20. American Scientific Publishers, in press.

20.

Konska G, Guillot J, De Latour M, Fonck Y. Expression of Tn antigen and N-acetyllactosamine residues in malignant and benign human breast tumors detected by lectins and monoclonal antibody 83D4. Int J Oncol. 1998;12(2):361–7.PubMed

21.

Bilder D, Schober M, Perrimon N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol. 2003;5(1):53–8.PubMed

22.

Macara IG. Par proteins: partners in polarization. Curr Biol. 2004;14(4):R160–2.PubMed

23.

Stucke VM, Timmerman E, Vandekerckhove J, Gevaert K, Hall A. The MAGUK protein MPP7 binds to the polarity protein hDlg1 and facilitates epithelial tight junction formation. Mol Biol Cell. 2007;18(5):1744–55.PubMed

24.

Fogg VC, Liu CJ, Margolis B. Multiple regions of Crumbs3 are required for tight junction formation in MCF10A cells. J Cell Sci. 2005;118(Pt 13):2859–69.PubMed

25.

Hurd TW, Gao L, Roh MH, Macara IG, Margolis B. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat Cell Biol. 2003;5(2):137–42.PubMed

26.

Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nat Cell Biol. 2000;2(8):540–7.PubMed

27.

Hutterer A, Betschinger J, Petronczki M, Knoblich JA. Sequential roles of Cdc42, Par-6, aPKC, and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Dev Cell. 2004;6(6):845–54.PubMed

28.

Sotillos S, Diaz-Meco MT, Caminero E, Moscat J, Campuzano S. DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila. J Cell Biol. 2004;166(4):549–57.PubMed

29.

Liu Y, Nusrat A, Schnell FJ, Reaves TA, Walsh S, Pochet M, et al. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci. 2000;113(Pt 13):2363–74.PubMed

30.

Ebnet K, Suzuki A, Horikoshi Y, Hirose T, Meyer Zu Brickwedde MK, Ohno S, et al. The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J. 2001;20(14):3738–48.PubMed

31.

Parkinson SJ, Le Good JA, Whelan RD, Whitehead P, Parker PJ. Identification of PKCzetaII: an endogenous inhibitor of cell polarity. EMBO J. 2004;23(1):77–88.PubMed

32.

Plachot C, Chaboub LS, Adissu HA, Wang L, Urazaev A, Sturgis J, et al. Factors necessary to produce basoapical polarity in human glandular epithelium formed in conventional and high-throughput three-dimensional culture: example of the breast epithelium. BMC Biol. 2009;7:77.PubMed

33.

McCaffrey LM, Macara IG. The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis. Genes Dev. 2009;23(12):1450–60.PubMed

34.

Pitelka DR, Hamamoto ST, Duafala JG, Nemanic MK. Cell contacts in the mouse mammary gland. I. Normal gland in postnatal development and the secretory cycle. J Cell Biol. 1973;56(3):797–818.PubMed

35.

Fischer A, Stuckas H, Gluth M, Russell TD, Rudolph MC, Beeman NE, et al. Impaired tight junction sealing and precocious involution in mammary glands of PKN1 transgenic mice. J Cell Sci. 2007;120(Pt 13):2272–83.PubMed

36.

Gateff E. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science. 1978;200(4349):1448–59.PubMed

37.

Jacob L, Opper M, Metzroth B, Phannavong B, Mechler BM. Structure of the l(2)gl gene of Drosophila and delimitation of its tumor suppressor domain. Cell. 1987;50(2):215–25.PubMed

38.

Bilder D, Li M, Perrimon N. Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science. 2000;289(5476):113–6.PubMed

39.

Lee SS, Weiss RS, Javier RT. Binding of human virus oncoproteins to hDlg/SAP97, a mammalian homolog of the Drosophila discs large tumor suppressor protein. Proc Natl Acad Sci U S A. 1997;94(13):6670–5.PubMed

40.

Hoover KB, Liao SY, Bryant PJ. Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity. Am J Pathol. 1998;153(6):1767–73.PubMed

41.

Nakagawa S, Huibregtse JM. Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Mol Cell Biol. 2000;20(21):8244–53.PubMed

42.

Chlenski A, Ketels KV, Korovaitseva GI, Talamonti MS, Oyasu R, Scarpelli DG. Organization and expression of the human zo-2 gene (tjp-2) in normal and neoplastic tissues. Biochim Biophys Acta. 2000;1493(3):319–24.PubMed

43.

Qiu RG, Abo A, Steven Martin G. A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation. Curr Biol. 2000;10(12):697–707.PubMed

44.

Glaunsinger BA, Weiss RS, Lee SS, Javier R. Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select interaction with the candidate tumor suppressor protein ZO-2. EMBO J. 2001;20(20):5578–86.PubMed

45.

Qin Y, Capaldo C, Gumbiner BM, Macara IG. The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J Cell Biol. 2005;171(6):1061–71.PubMed

46.

Polette M, Gilles C, Nawrocki-Raby B, Lohi J, Hunziker W, Foidart JM, et al. Membrane-type 1 matrix metalloproteinase expression is regulated by zonula occludens-1 in human breast cancer cells. Cancer Res. 2005;65(17):7691–8.PubMed

47.

Etienne-Manneville S. Polarity proteins in migration and invasion. Oncogene. 2008;27(55):6970–80.PubMed

48.

Brumby AM, Richardson HE. Scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 2003;22(21):5769–79.PubMed

49.

Dow LE, Brumby AM, Muratore R, Coombe ML, Sedelies KA, Trapani JA, et al. hScrib is a functional homologue of the Drosophila tumour suppressor Scribble. Oncogene. 2003;22(58):9225–30.PubMed

50.

Petit MM, Meulemans SM, Alen P, Ayoubi TA, Jansen E, Van de Ven WJ. The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus. BMC Cell Biol. 2005;6(1):1.PubMed

51.

Gardiol D, Kuhne C, Glaunsinger B, Lee SS, Javier R, Banks L. Oncogenic human papillomavirus E6 proteins target the discs large tumour suppressor for proteasome-mediated degradation. Oncogene. 1999;18(40):5487–96.PubMed

52.

Dow LE, Kauffman JS, Caddy J, Zarbalis K, Peterson AS, Jane SM, et al. The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene. 2007;26(16):2272–82.PubMed

53.

Underwood JM, Imbalzano KM, Weaver VM, Fischer AH, Imbalzano AN, Nickerson JA. The ultrastructure of MCF-10A acini. J Cell Physiol. 2006;208(1):141–8.PubMed

54.

Zhan L, Rosenberg A, Bergami KC, Yu M, Xuan Z, Jaffe AB, et al. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell. 2008;135(5):865–78.PubMed

55.

Aranda V, Haire T, Nolan ME, Calarco JP, Rosenberg AZ, Fawcett JP, et al. Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nat Cell Biol. 2006;8(11):1235–45.PubMed

56.

Reichert M, Muller T, Hunziker W. The PDZ domains of zonula occludens-1 induce an epithelial to mesenchymal transition of Madin-Darby canine kidney I cells. Evidence for a role of beta-catenin/Tcf/Lef signaling. J Biol Chem. 2000;275(13):9492–500.PubMed

57.

Sommers CL, Byers SW, Thompson EW, Torri JA, Gelmann EP. Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res Treat. 1994;31(2–3):325–35.PubMed

58.

Chandramouly G, Abad PC, Knowles DW, Lelievre SA. The control of tissue architecture over nuclear organization is crucial for epithelial cell fate. J Cell Sci. 2007;120(Pt 9):1596–606.PubMed

59.

Mantovani F, Massimi P, Banks L. Proteasome-mediated regulation of the hDlg tumour suppressor protein. J Cell Sci. 2001;114(Pt 23):4285–92.PubMed

60.

Pagliarini RA, Xu T. A genetic screen in Drosophila for metastatic behavior. Science. 2003;302(5648):1227–31.PubMed

61.

Nakagawa S, Yano T, Nakagawa K, Takizawa S, Suzuki Y, Yasugi T, et al. Analysis of the expression and localisation of a LAP protein, human scribble, in the normal and neoplastic epithelium of uterine cervix. Br J Cancer. 2004;90(1):194–9.PubMed

62.

Lee CW, Simin K, Liu Q, Plescia J, Guha M, Khan A, et al. A functional Notch-survivin gene signature in basal breast cancer. Breast Cancer Res. 2008;10(6):R97.PubMed

63.

Dontu G, El-Ashry D, Wicha MS. Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol Metab. 2004;15(5):193–7.PubMed

64.

Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson NG, et al. Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst. 2007;99(8):616–27.PubMed

65.

Yamaguchi M, Hirose F, Inoue YH, Ohno K, Yoshida H, Hayashi Y, et al. Genetic link between p53 and genes required for formation of the zonula adherens junction. Cancer Sci. 2004;95(5):436–41.PubMed

66.

Petit MM, Fradelizi J, Golsteyn RM, Ayoubi TA, Menichi B, Louvard D, et al. LPP, an actin cytoskeleton protein related to zyxin, harbors a nuclear export signal and transcriptional activation capacity. Mol Biol Cell. 2000;11(1):117–29.PubMed

67.

Grunewald TG, Pasedag SM, Butt E. Cell adhesion and transcriptional activity—defining the role of the novel protooncogene LPP. Transl Oncol. 2009;2(3):107–16.PubMed

68.

Guo B, Sallis RE, Greenall A, Petit MM, Jansen E, Young L, et al. The LIM domain protein LPP is a coactivator for the ETS domain transcription factor PEA3. Mol Cell Biol. 2006;26(12):4529–38.PubMed

69.

Ishidate T, Matsumine A, Toyoshima K, Akiyama T. The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Oncogene. 2000;19(3):365–72.PubMed

70.

Kouzmenko AP, Takeyama K, Kawasaki Y, Akiyama T, Kato S. Truncation mutations abolish chromatin-associated activities of adenomatous polyposis coli. Oncogene. 2008;27(36):4888–99.PubMed

71.

Nolan ME, Aranda V, Lee S, Lakshmi B, Basu S, Allred DC, et al. The polarity protein Par6 induces cell proliferation and is overexpressed in breast cancer. Cancer Res. 2008;68(20):8201–9.PubMed

72.

Milde-Langosch K, Bamberger AM, Rieck G, Grund D, Hemminger G, Muller V, et al. Expression and prognostic relevance of activated extracellular-regulated kinases (ERK1/2) in breast cancer. Br J Cancer. 2005;92(12):2206–15.PubMed

73.

Dunn KL, Espino PS, Drobic B, He S, Davie JR. The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling. Biochem Cell Biol. 2005;83(1):1–14.PubMed

74.

Lim JH, Catez F, Birger Y, West KL, Prymakowska-Bosak M, Postnikov YV, et al. Chromosomal protein HMGN1 modulates histone H3 phosphorylation. Mol Cell. 2004;15(4):573–84.PubMed

75.

Mishra SK, Mandal M, Mazumdar A, Kumar R. Dynamic chromatin remodeling on the HER2 promoter in human breast cancer cells. FEBS Lett. 2001;507(1):88–94.PubMed

76.

Chadee DN, Taylor WR, Hurta RA, Allis CD, Wright JA, Davie JR. Increased phosphorylation of histone H1 in mouse fibroblasts transformed with oncogenes or constitutively active mitogen-activated protein kinase kinase. J Biol Chem. 1995;270(34):20098–105.PubMed

77.

Taylor WR, Chadee DN, Allis CD, Wright JA, Davie JR. Fibroblasts transformed by combinations of ras, myc and mutant p53 exhibit increased phosphorylation of histone H1 that is independent of metastatic potential. FEBS Lett. 1995;377(1):51–3.PubMed

78.

Chadee DN, Hendzel MJ, Tylipski CP, Allis CD, Bazett-Jones DP, Wright JA, et al. Increased Ser-10 phosphorylation of histone H3 in mitogen-stimulated and oncogene-transformed mouse fibroblasts. J Biol Chem. 1999;274(35):24914–20.PubMed

79.

Stevenson BR, Keon BH. The tight junction: morphology to molecules. Annu Rev Cell Dev Biol. 1998;14:89–109.PubMed

80.

Balda MS, Garrett MD, Matter K. The ZO-1-associated Y-box factor ZONAB regulates epithelial cell proliferation and cell density. J Cell Biol. 2003;160(3):423–32.PubMed

81.

Ladomery M, Sommerville J. A role for Y-box proteins in cell proliferation. Bioessays. 1995;17(1):9–11.PubMed

82.

Kavanagh E, Buchert M, Tsapara A, Choquet A, Balda MS, Hollande F, et al. Functional interaction between the ZO-1-interacting transcription factor ZONAB/DbpA and the RNA processing factor symplekin. J Cell Sci. 2006;119(Pt 24):5098–105.PubMed

83.

Sourisseau T, Georgiadis A, Tsapara A, Ali RR, Pestell R, Matter K, et al. Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Mol Cell Biol. 2006;26(6):2387–98.PubMed

84.

Sharp JA, Mailer SL, Thomson PC, Lefevre C, Nicholas KR. Identification and transcript analysis of a novel wallaby (Macropus eugenii) basal-like breast cancer cell line. Mol Cancer. 2008;7:1.PubMed

85.

Milde-Langosch K. The Fos family of transcription factors and their role in tumourigenesis. Eur J Cancer. 2005;41(16):2449–61.PubMed

86.

Zahnow CA. CCAAT/enhancer-binding protein beta: its role in breast cancer and associations with receptor tyrosine kinases. Expert Rev Mol Med. 2009;11:e12.PubMed

87.

Betanzos A, Huerta M, Lopez-Bayghen E, Azuara E, Amerena J, Gonzalez-Mariscal L. The tight junction protein ZO-2 associates with Jun, Fos and C/EBP transcription factors in epithelial cells. Exp Cell Res. 2004;292(1):51–66.PubMed

88.

Gottardi CJ, Arpin M, Fanning AS, Louvard D. The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. Proc Natl Acad Sci U S A. 1996;93(20):10779–84.PubMed

89.

Gonzalez-Mariscal L, Namorado MC, Martin D, Luna J, Alarcon L, Islas S, et al. Tight junction proteins ZO-1, ZO-2, and occludin along isolated renal tubules. Kidney Int. 2000;57(6):2386–402.PubMed

90.

Traweger A, Fuchs R, Krizbai IA, Weiger TM, Bauer HC, Bauer H. The tight junction protein ZO-2 localizes to the nucleus and interacts with the heterogeneous nuclear ribonucleoprotein scaffold attachment factor-B. J Biol Chem. 2003;278(4):2692–700.PubMed

91.

Nayler O, Stratling W, Bourquin JP, Stagljar I, Lindemann L, Jasper H, et al. SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. Nucleic Acids Res. 1998;26(15):3542–9.PubMed

92.

Townson SM, Sullivan T, Zhang Q, Clark GM, Osborne CK, Lee AV, et al. HET/SAF-B overexpression causes growth arrest and multinuclearity and is associated with aneuploidy in human breast cancer. Clin Cancer Res. 2000;6(9):3788–96.PubMed

93.

Oesterreich S. Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis? J Cell Biochem. 2003;90(4):653–61.PubMed

94.

Debril MB, Dubuquoy L, Feige JN, Wahli W, Desvergne B, Auwerx J, et al. Scaffold attachment factor B1 directly interacts with nuclear receptors in living cells and represses transcriptional activity. J Mol Endocrinol. 2005;35(3):503–17.PubMed

95.

Huerta M, Munoz R, Tapia R, Soto-Reyes E, Ramirez L, Recillas-Targa F, et al. Cyclin D1 is transcriptionally down-regulated by ZO-2 via an E box and the transcription factor c-Myc. Mol Biol Cell. 2007;18(12):4826–36.PubMed

96.

Traweger A, Lehner C, Farkas A, Krizbai IA, Tempfer H, Klement E, et al. Nuclear Zonula occludens-2 alters gene expression and junctional stability in epithelial and endothelial cells. Differentiation. 2008;76(1):99–106.PubMed

97.

Garcia-Mata R, Dubash AD, Sharek L, Carr HS, Frost JA, Burridge K. The nuclear RhoA exchange factor Net1 interacts with proteins of the Dlg family, affects their localization, and influences their tumor suppressor activity. Mol Cell Biol. 2007;27(24):8683–97.PubMed

98.

Borden KL. Pondering the promyelocytic leukemia protein (PML) puzzle: possible functions for PML nuclear bodies. Mol Cell Biol. 2002;22(15):5259–69.PubMed

99.

Kausalya PJ, Phua DC, Hunziker W. Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: binding to PDZ-domain proteins and cell-cell adhesion regulate plasma membrane and nuclear localization of ARVCF. Mol Biol Cell. 2004;15(12):5503–15.PubMed

100.

Bit-Avragim N, Rohr S, Rudolph F, Van der Ven P, Furst D, Eichhorst J, et al. Nuclear localization of the zebrafish tight junction protein nagie oko. Dev Dyn. 2008;237(1):83–90.PubMed

101.

Cline EG, Nelson WJ. Characterization of mammalian Par 6 as a dual-location protein. Mol Cell Biol. 2007;27(12):4431–43.PubMed

102.

Fang L, Wang Y, Du D, Yang G, Tak Kwok T, Kai Kong S, et al. Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair. Cell Res. 2007;17(2):100–16.PubMed

103.

Boheler KR. Stem cell pluripotency: a cellular trait that depends on transcription factors, chromatin state and a checkpoint deficient cell cycle. J Cell Physiol. 2009;221(1):10–7.PubMed

104.

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.PubMed

105.

Isfort RJ, Cody DB, Stuard SB, Ridder GM, LeBoeuf RA. Calcium functions as a transcriptional and mitogenic repressor in Syrian hamster embryo cells: roles of intracellular pH and calcium in controlling embryonic cell differentiation and proliferation. Exp Cell Res. 1996;226(2):363–71.PubMed

106.

Tsukita S, Yamazaki Y, Katsuno T, Tamura A. Tight junction-based epithelial microenvironment and cell proliferation. Oncogene. 2008;27(55):6930–8.PubMed

Title: Tissue Polarity-Dependent Control of Mammary Epithelial Homeostasis and Cancer Development: an Epigenetic Perspective
Author: Sophie A. Lelièvre
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/s10911-010-9168-y

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

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2010

The Role of Histone Modifications and Variants in Regulating Gene Expression in Breast Cancer

Breast Cancer Epigenetics: From DNA Methylation to microRNAs

Epigenetic Regulation of Milk Production in Dairy Cows

The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

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

Epigenetic Regulation in Estrogen Receptor Positive Breast Cancer—Role in Treatment Response

Keynote webinar | Spotlight on antibody–drug conjugates in cancer