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Notch Signaling in Mammary Gland Tumorigenesis

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The Notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. Recent studies suggest that, depending on the cellular and developmental context, Notch signaling may also affect cell proliferation and programmed cell death. Mammals have four related Notch genes. One of these, designated Notch-4, was found to be a common integration site for the mouse mammary tumor virus in mouse mammary tumors. One consequence of this type of viral integration event is the ectopic expression of the intracellular domain of Notch-4 that corresponds to a gain-of-function mutation. Expression of “activated” Notch-4 in mammary epithelium has profound effects on mammary gland development and tumorigenesis. In this review, we briefly summarize the structure and function of the Notch receptor, as well as the components that comprise and modify the signaling pathway. Finally we discuss the potential role of Notch in mammary gland development and tumorigenesis.

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REFERENCES

  1. O. L. Moohr (1919). Character changes caused by mutation of an entire region of a chromosome in Drosophila. Genetics 4:275–282.

    Google Scholar 

  2. L. Miele and B. Osborne (1999). Arbiter of differentiation and death: Notch signaling meets apoptosis. J. Cell Physiol. 181:393–409.

    Google Scholar 

  3. B. Osborne and L. Miele (1999). Notch and the immune system. Immunity 11:653–663.

    Google Scholar 

  4. N. E. Baker (2000). Notch signaling in the nervous system. Pieces still missing from the puzzle. Bioessays 22:264–273.

    Google Scholar 

  5. S. Artavanis-Tsakonas, M. D. Rand, and R. J. Lake (1999). Notch signaling: Cell fate control and signal integration in development. Science 284:770–776.

    Google Scholar 

  6. L. A. Milner and A. Bigas (1999). Notch as a mediator of cell fate determination in hematopoiesis: Evidence and speculation. Blood 93:2431–2448.

    Google Scholar 

  7. M. Lardelli, R. Williams, and U. Lendahl (1995). Notch-related genes in animal development. Int. J. Dev. Biol. 39:769–780.

    Google Scholar 

  8. E. M. Maine, J. L. Lissemore, and W. T. Starmer (1995). A phylogenetic analysis of vertebrate and invertebrate Notch-related genes. Mol. Phylogenet. Evol. 4:139–149.

    Google Scholar 

  9. D. Gallahan and R. Callahan (1997). The mouse mammary tumor associated gene INT-3 is a unique member of the NOTCH gene family (NOTCH4). Oncogene 14:1883–1890.

    Google Scholar 

  10. J. Robbins, B. J. Blondel, D. Gallahan, and R. Callahan (1992). Mouse mammary tumor gene Int-3: A member of the Notch gene family transforms mammary epithelial cells. J. Virol. 66:2594–2599.

    Google Scholar 

  11. H. Uyttendaele, G. Marazzi, G. Wu, Q. Yan, D. Sassoon, and J. Kitajewski (1996). Notch4/int-3, amammaryproto-oncogene, is an endothelial cell-specific mammalian Notch gene. Development 122:2251–2259.

    Google Scholar 

  12. D. Gallahan, C. Kozak, and R. Callahan (1987). Anew common integration region (int-3) for mouse mammary tumor virus on mouse chromosome 17. J. Virol. 61:218–220.

    Google Scholar 

  13. L. D. Siracusa, M. H. Rosner, M. A. Vigano, D. J. Gilbert, L. M. Staudt, N. G. Copeland, and N. A. Jenkins. (1991). Chromosomal location of the octamer transcription factors, Otf-1, Otf-2, and Otf-3, defines multiple Otf-3-related sequences dispersed in the mouse genome. Genomics 10:313–326.

    Google Scholar 

  14. I. Rebay, R. G. Fehon, and S. Artavanis-Tsakonas (1993). Specific truncations of Notch define dominant activated and dominant negative forms of the receptor. Cell 74:319–329.

    Google Scholar 

  15. G. Struhl, K. Fitzgerald, and I. Greenwald (1993). Intrinsic activity of the lin-12 and Notch intracellular domains in vivo. Cell 74:331–345.

    Google Scholar 

  16. D. Gallahan and R. Callahan (1987). Mammary tumorigenesis in feral mice: Identification of a new int locus in mouse mammary tumor virus(CzechII)-induced mammary tumors. J. Virol. 61:66–74.

    Google Scholar 

  17. N. H. Sarkar, S. Haga, A. F. Lehner, W. Zhao, S. Imai, and K. Moriwaki (1994). Insertional mutation of int protooncogenes in the mammary tumors of a new strain of mice derived from the wild in China: Normal-and tumor-tissue-specific expression of int-3 transcripts. Virology 203:52–62.

    Google Scholar 

  18. G. Peters (1990). Oncogenes at viral integration sites. Cell Growth Differ. 1:503–510.

    Google Scholar 

  19. A. Dievart, N. Beaulieu, and P. Jolicoeur (1999). Involvement of Notch1 in the development of mouse mammary tumors. Oncogene 18:5973–5981.

    Google Scholar 

  20. S. Artavanis-Tsakonas, K. Matsuno, and M. E. Fortini (1995). Notch signaling. Science 268:225–232.

    Google Scholar 

  21. K. Tamura, Y. Taniguchi, S. Minoguchi, Y. Sakai, T. Tun, T. Furukawa, and T. Honjo (1995). Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-Jκ/Su(H). Curr. Biol. 5:1416–1423.

    Google Scholar 

  22. F. Logeat, C. Bessia, C. Brou, O. LeBail, S. Jarriault, N. G. Seidah, and A. Israel (1998). The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc. Natl. Acad. Sci. U.S.A. 95:8108–8112.

    Google Scholar 

  23. G. Weinmaster (1997). The ins and outs of notch signaling. Mol. Cell Neurosci. 9:91–102.

    Google Scholar 

  24. S. L. Dunwoodie, D. Henrique, S. M. Harrison, and R. S. Beddington (1997). Mouse Dll3: A novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo. Development 124:3065–3076.

    Google Scholar 

  25. B. Bettenhausen, M. Hrabe de Angelis, D. Simon, J. L. Guenet, and A. Gossler (1995). Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta. Development 121:2407–2418.

    Google Scholar 

  26. G. E. Gray, R. S. Mann, E. Mitsiadis, D. Henrique, M. L. Carcangiu, A. Banks, J. Leiman, D. Ward, D. Ish-Horowitz, and S. Artavanis-Tsakonas (1999). Human ligands of the Notch receptor. Am. J. Pathol. 154:785–794.

    Google Scholar 

  27. L. Li, L. A. Milner, Y. Deng, M. Iwata, A. Banta, L. Graf, S. Marcovina, C. Friedman, B. J. Trask, L. Hood, and B. Torok-Storb (1998). The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity 8:43–55.

    Google Scholar 

  28. K. M. Klueg, T. R. Parody, and M. A. Muskavitch (1998). Complex proteolytic processing acts on Delta, a transmembrane ligand for Notch, during Drosophila development. Mol. Biol. Cell. 9:1709–1723.

    Google Scholar 

  29. H. Qi, M. D. Rand, X. Wu, N. Sestan, W. Wang, P. Rakic, T. Xu, and S. Artavanis-Tsakonas (1999). Processing of the notch ligand delta by the metalloprotease Kuzbanian. Science 283:91–94.

    Google Scholar 

  30. I. Rebay, R. J. Fleming, R. G. Fehon, L. Cherbas and S. Artavanis-Tsakonas (1991). Specific EGF repeats of Notch mediate interactions with Delta and Serrate: Implications for Notch as a multifunctional receptor. Cell 67:687–699.

    Google Scholar 

  31. C. Brou, F. Logeat, N. Gupta, C. Bessia, O. LeBail, J. R. Doedens, A. Cumano, P. Roux, R. A. Black, and A. Israel (2000). A novel proteolytic cleavage involved in Notch signaling: The role of the disintegrin-metalloprotease TACE. Mol. Cell. 5:207–216.

    Google Scholar 

  32. J. S. Mumm, E. H. Schroeter, M. T. Saxena, A. Griesemer, X. Tian, D. J. Pan, W. J. Ray and R. Kopan (2000). A ligandinduced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol. Cell. 5:197–206.

    Google Scholar 

  33. J. C. Aster, E. S. Robertson, R. P. Hasserjian, J. R. Turner, E. Kief, and J. Sklar (1997). Oncogenic forms ofNOTCH1lacking either the primary binding site for RBP-Jkappa or nuclear localization sequences retain the ability to associate with RBPJkappa and activate transcription. J. Biol. Chem. 272:11336–11343.

    Google Scholar 

  34. H. Y. Kao, P. Ordentlich, N. Koyano-Nakagawa, Z. Tang, M. Downes, C. R. Kintner, R.M. Evans, and T. Kadesch (1998). Ahistone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev. 12:2269–2277.

    Google Scholar 

  35. S. Zhou, M. Fujimuro, J. J. Hsieh, L. Chen, A. Miyamoto, G. Weinmaster, and S. D. Hayward (2000). SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function. Mol. Cell Biol. 20:2400–2410.

    Google Scholar 

  36. S. Stifani, C. M. Blaumueller, N. J. Redhead, R. E. Hill, and S. Artavanis-Tsakonas (1992). Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins [published erratum appears in Nat. Genet. 2(4):343]. Nat. Genet. 2:119–127.

    Google Scholar 

  37. S. Jarriault, C. Brou, F. Logeat, E. H. Schroeter, R. Kopan, and A. Israel (1995). Signaling downstream of activated mammalian NOTCH. Nature 377:355–358.

    Google Scholar 

  38. S. Goodbourn (1995). Signal transduction. Notch takes a short cut [news; comment]. Nature 377:288–289.

    Google Scholar 

  39. F. Oswald, S. Liptay, G. Adler, and R. M. Schmid (1998). NF-κB2 is a putative target gene of activated Notch-1 via RBPJκ. Mol. Cell Biol. 18:2077–2088.

    Google Scholar 

  40. A. M. Bailey and J. W. Posakony, (1995). Suppressor of Hairless directly activates transcription of enhancer of slit complex genes in response to NOTCH receptor activity. Genes Dev. 9:2609–2622.

    Google Scholar 

  41. P. Heitzler, M. Bourouis, L. Ruel, C. Carteret, and P. Simpson (1996). Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signaling in Drosophila. Development 122:161–171.

    Google Scholar 

  42. C. Shawber, D. Nofziger, J. J. Hsieh, C. Lindsell, O. Bogler, D. Hayward, and G. Weinmaster (1996). Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway. Development 122:3765–3773.

    Google Scholar 

  43. K. Matsuno, M. J. Go, X. Sun, D. S. Eastman, and S. Artavanis-Tsakonas (1997). Suppressor of hairless-independent events in Notch signaling imply novel pathway elements. Development 124:4265–4273.

    Google Scholar 

  44. P. Ordentlich, A. Lin, C. P. Shen, C. Blaumueller, K. Matsuno, S. Artavanis-Tsakonas, and T. Kadesch (1998). Notch inhibition of E47 supports the existence of a novel signaling pathway. Mol. Cell Biol. 18:2230–2239.

    Google Scholar 

  45. K. Matsuno, D. Eastman, T. Mitsiades, A. M. Quinn, M. L. Carcanciu, P. Ordentlich, T. Kadesch, and S. Artavanis-Tsakonas (1998). Human deltex is a conserved regulator of Notch signaling. Nat. Genet. 19:74–78.

    Google Scholar 

  46. E. Guan, J. Wang, J. Laborda, M. Norcross, P. A. Baeuerle, and T. Hoffman (1996). T cell leukemia-associated human Notch/translocation-associated Notch homologue has Iκ B-like activity and physically interacts with nuclear factor-κ Bproteins in T cells. J. Exp. Med. 183:2025–2032.

    Google Scholar 

  47. B. M. Jehn, W. Bielke, W. S. Pear, and B. A. Osborne (1999). Cutting edge: Protective effects of notch-1 on TCR-induced apoptosis. J. Immunol. 162:635–638.

    Google Scholar 

  48. E. Giniger (1998). A role for Abl in Notch signaling. Neuron. 20:667–681.

    Google Scholar 

  49. N. Carlesso, J.C. Aster, J. Sklar and D.T. Scadden (1999). Notch-1-induced delay of human hematopoietic progenitor cell differentiation is associated with altered cell cycle kinetics. Blood 93:838–848.

    Google Scholar 

  50. T. Washburn, E. Schweighoffer, T. Gridley, D. Chang, B. J. Fowlkes, D. Cado and E. Robey (1997). Notch activity influences the αβ versus γδ T cell lineage decision. Cell 88:833–843.

    Google Scholar 

  51. E. Robey, D. Chang, A. Itano, D. Cado, H. Alexander, D. Lans, G. Weinmaster, and P. Salmon (1996). An activated form of Notch influences the choice between CD4 and CD8 T cell lineages. Cell 87:483–492.

    Google Scholar 

  52. C. Garces, M. J. Ruiz-Hidalgo, J. F. de Mora, C. Park, L. Miele, J. Goldstein, E. Bonvini, A. Porras, and J. Laborda (1997). Notch-1 controls the expression of fatty acid-activated transcription factors and is required for adipogenesis. J. Biol. Chem. 272:29729–29734.

    Google Scholar 

  53. M. L. Deftos, Y. W. He, E. W. Ojala, and M. J. Bevan (1998). Correlating notch signaling with thymocyte maturation. Immunity 9:777–786.

    Google Scholar 

  54. P. Simpson (1997). Notch signaling in development. Perspect Dev. Neurobiol. 4:297–304.

    Google Scholar 

  55. V. M. Panin and K. D. Irvine (1998). Modulators of Notch signaling. Semin. Cell Dev. Biol. 9:609–617.

    Google Scholar 

  56. V. M. Panin, V. Papayannopoulos, R. Wilson and K. D. Irvine (1997). Fringe modulates Notch-ligand interactions. Nature 387:908–912.

    Google Scholar 

  57. R. J. Fleming, Y. Gu, and N. A. Hukriede (1997). Serratemediated activation of Notch is specifically blocked by the product of the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc. Development 124:2973–2981.

    Google Scholar 

  58. Y. P. Yuan, J. Schultz, M. Mlodzik, and P. Bork (1997). Secreted fringe-like signaling molecules may be glycosyltransferases [letter]. Cell 88:9–11.

    Google Scholar 

  59. J. F. de Celis and S. J. Bray (2000). The Abruptex domain of Notch regulates negative interactions between Notch, its ligands and Fringe. Development 127:1291–1302.

    Google Scholar 

  60. B. Lu, L. Y. Jan, and Y. N. Jan (1998). Asymmetric cell division: Lessons from flies and worms. Curr. Opin. Genet. Dev. 8:392–399.

    Google Scholar 

  61. E. P. Spana and C. Q. Doe (1996). Numb antagonizes Notch signaling to specify sibling neuron cell fates. Neuron. 17:21–26.

    Google Scholar 

  62. M. Guo, L. Y. Jan, and Y. N. Jan (1996). Control of daughter cell fates during asymmetric division: Interaction of Numb and Notch. Neuron. 17:27–41.

    Google Scholar 

  63. P. Bork and B. Margolis (1995). A phosphotyrosine interaction domain [letter]. Cell 80:693–694.

    Google Scholar 

  64. W. Zhong, J. N. Feder, M-M. Jiang, L. Y. Jan, and Y. N. Jan (1996). Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis. Neuron. 17:43–53.

    Google Scholar 

  65. A. Chenn and S. K. McConnell (1995). Cleavage orientation and the asymmetric inheritance of Notch-1 immunoreactivity in mammalian neurogenesis. Cell 82:631–641.

    Google Scholar 

  66. S. Wang, S. Younger-Shepherd, L. Y. Jan, and Y. N. Jan (1997). Only a subset of the binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless. Development 124:4435–4446.

    Google Scholar 

  67. C. Jhappan, D. Gallahan, C. Stahle, E. Chu, G. H. Smith, G. Merlino, and R. Callahan (1992). Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev. 6:345–355.

    Google Scholar 

  68. G. H. Smith, D. Gallahan, F. Diella, C. Jhappan, G. Merlino, and R. Callahan (1995). Constitutive expression of a truncated INT3 gene in mouse mammary epithelium impairs differentiation and functional development. Cell Growth Differ. 6:563–577.

    Google Scholar 

  69. D. Gallahan, C. Jhappan, G. Robinson, L. Hennighausen, R. Sharp, E. Kordon, R. Callahan, G. Merlino, and G. H. Smith (1996). Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis. Cancer Res. 56:1775–1785.

    Google Scholar 

  70. G. Chepko and G. H. Smith (1997). Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal. Tissue Cell 29:239–253.

    Google Scholar 

  71. P. Simpson (1994). The Notch Receptors. R. G. Landes Company, Austin, Texas.

    Google Scholar 

  72. S. Artavanis-Tsakonas (1997). Alagille syndrome—a notch up for the Notch receptor [news; comment]. Nat Genet. 16:212–213.

    Google Scholar 

  73. A. Joutel and E. Tournier-Lasserve (1998). Notch signalling pathway and human diseases. Semin. Cell Dev. Biol. 9:619–625.

    Google Scholar 

  74. N. A. Hukriede, Y. Gu and R. J. Fleming (1997). A dominantnegative form of Serrate acts as a general antagonist of Notch activation. Development 124:3427–3437.

    Google Scholar 

  75. X. Sun and S. Artavanis-Tsakonas (1997). Secreted forms of DELTA and SERRATE define antagonists of Notch signaling in Drosophila. Development 124:3439–3448.

    Google Scholar 

  76. M. Lardelli, J. Dahlstrand, and U. Lendahl (1994). The novel Notch homologue mouse Notch 3 lacks specific epidermal growth factor-repeats and is expressed in proliferating neuroepithelium. Mech. Dev. 46:123–136.

    Google Scholar 

  77. P. J. Swiatek, C. E. Lindsell, F. F. del Amo, G. Weinmaster, and T. Gridley (1994). Notch1 is essential for postimplantation development in mice. Genes Dev. 8:707–719.

    Google Scholar 

  78. Y. Xue, X. Gao, C. E. Lindsell, C. R. Norton, B. Chang, C. Hicks, M. Gendron-Maguire, E. B. Rand, G. Weinmaster, and T. Gridley (1999). Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Human Mol. Genet. 8:723–730.

    Google Scholar 

  79. C. Oka, T. Nakano, A. Wakeham, J. L. de la Pompa, C. Mori, T. Sakai, S. Okazaki, M. Kawaichi, K. Shiota, T. W. Mak, and T. Honjo (1995). Disruption of the mouse RBP-J kappa gene results in early embryonic death. Development 121:3291–3301.

    Google Scholar 

  80. R. Jiang, Y. Lan, H. D. Chapman, C. Shawber, C. R. Norton, D. V. Serreze, G. Weinmaster, and T. Gridley (1998). Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. Genes Dev. 12:1046–1057.

    Google Scholar 

  81. M. Hrabe de Angelis, J. McIntyre, 2nd, and A. Gossler (1997). Maintenance of somite borders in mice requires the Delta homologue DII1. Nature 386:717–721.

    Google Scholar 

  82. Y. Hamada, Y. Kadokawa, M. Okabe, M. Ikawa, J. R. Coleman, and Y. Tsujimoto (1999). Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development 126:3415–3424.

    Google Scholar 

  83. J. L. de la Pompa, A. Wakeham, K. M. Correia, E. Samper, S. Brown, R. J. Aguilera, T. Nakano, T. Honjo, T. W. Mak, J. Rossant, and R. A. Conlon (1997). Conservation of the Notch signaling pathway in mammalian neurogenesis. Development 124:1139–1148.

    Google Scholar 

  84. R. A. Conlon, A. G. Reaume, and J. Rossant (1995). Notch1 is required for the coordinate segmentation of somites. Development 121:1533–1545.

    Google Scholar 

  85. L. T. Krebs, Y. Xue, C.R. Norton, J. R. Shutter, M. Maguire, J. P. Sundberg, D. Gallahan, V. Closson, J. Kitajewski, R. Callahan, G. H. Smith, K. L. Stark, and T. Gridley (2000). Notch signaling is essential for vascular morphogenesis in mice. [in process citation]. Genes Dev. 14:1343–1352.

    Google Scholar 

  86. J. Aster, W. Pear, R. Hasserjian, H. Erba, F. Davi, B. Luo, M. Scott, D. Baltimore, and J. Sklar (1994). Functional analysis of the TAN-1 gene, a human homolog of Drosophila Notch, Cold Spring Harbor Symp. Quant. Biol. 59:125–136.

    Google Scholar 

  87. L.W. Ellison, J. Bird, D. C. West, A. L. Soreng, T. C. Reynolds, S. D. Smith, and J. Sklar (1991). TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T Lymphoblastic neoplasms. Cell 66:649–661.

    Google Scholar 

  88. L. Girard, Z. Hanna, N. Beaulieu, C. D. Hoemann, C. Simard, C. A. Kozak, and P. Jolicoeur (1996). Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis. Genes Dev. 10:1930–1944.

    Google Scholar 

  89. J. L. Rohn, A. S. Lauring, M. L. Linenberger, and J. Overbaugh (1996). Transduction of Notch2 in feline leukemia virusinduced thymic lymphoma. J. Virol. 70:8071–8080.

    Google Scholar 

  90. A. J. Capobianco, P. Zagouras, C.M. Blaumueller, S. Artavanis-Tsakonas, and J. M. Bishop (1997). Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2. Mol. Cell Biol. 17:6265–6273.

    Google Scholar 

  91. P. Zagouras, S. Stifani, C. M. Blaumueller, M. L. Carcangiu, and S. Artavanis-Tsakonas (1995). Alterations in Notch signaling in neoplastic lesions of the human cervix. Proc. Natl. Acad. Sci. U.S.A. 92:6414–6418.

    Google Scholar 

  92. A. Imatani and R. Callahan (2000). Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines. Oncogene 19:223–231.

    Google Scholar 

  93. J. D. Axelrod, K. Matsuno, S. Artavanis-Tsakonas, and N. Perrimon (1996). Interaction between wingless and Notch signaling pathways mediated by dishevelled. Science 271:1826–1832.

    Google Scholar 

  94. H. Dierick and A. Bejsovec (1999). Cellular mechanisms of wingless/Wnt signal transduction. Curr. Top. Dev. Biol. 43:153–190.

    Google Scholar 

  95. H. Uyttendaele, J. V. Soriano, R. Montesano, and J. Kitajewski (1998). Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion. Dev. Biol. 196:204–217.

    Google Scholar 

  96. J. V. Soriano, H. Uyttendaele, J. Kitajewski, and R. Montesano (2000). Expression of an activated Notch4(int-3) oncoprotein disrupts morphogenesis and induces an invasive phenotype in mammary epithelial cells in vitro. Int. J. Cancer. 86:652–659.

    Google Scholar 

  97. C. S. Wesley (1999). Notch and wingless regulate expression of cuticle patterning genes. Mol. Cell Biol. 19:5743–5758.

    Google Scholar 

  98. C. S. Wesley and L. Saez (2000). Notch responds differently to Delta and wingless in cultured Drosophila cells. J. Biol. Chem. 275:9099–9101.

    Google Scholar 

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Callahan, R., Raafat, A. Notch Signaling in Mammary Gland Tumorigenesis. J Mammary Gland Biol Neoplasia 6, 23–36 (2001). https://doi.org/10.1023/A:1009512414430

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