Notch signaling in mammary gland tumorigenesis.
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.
Callahan
R
R
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892, USA. rc54d@nih.gov
Raafat
A
A
D000818:Animals; D001940:Breast / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008024:Ligands; D008321:Mammary Glands, Animal / Q000196:embryology / Q000254:growth & development*; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D011991:Receptors, Virus; D015398:Signal Transduction / Q000502:physiology*
D004268:DNA-Binding Proteins; C111417:Fam89b protein, mouse; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008024:Ligands; D008565:Membrane Proteins; C106075:NOTCH4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497570:RBPJ protein, human; C497571:Rbpj protein, mouse; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D011991:Receptors, Virus