CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smith, G. H.
Right arrow Articles by Callahan, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, G. H.
Right arrow Articles by Callahan, R.

Cell Growth & Differentiation, Vol 6, Issue 5 563-577, Copyright © 1995 by American Association of Cancer Research


ARTICLES

Constitutive expression of a truncated INT3 gene in mouse mammary epithelium impairs differentiation and functional development

GH Smith, D Gallahan, F Diella, C Jhappan, G Merlino and R Callahan
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-1750, USA.

INT3 is interrupted by retroviral DNA insertion in approximately 18% of primary Czech mouse mammary tumors induced by mouse mammary tumor virus. One consequence of these insertions is the production of a 2.4-kilobase, tumor-specific RNA transcript encoding the entire intracellular domain of the Int3 protein which is initiated from the 3' long terminal repeat promoter of the inserted viral genome. Female mice (FVB-3) transgenic for a genomic fragment comprised of this truncated region of INT3 express the 2.4-kilobase truncated INT3 transcript and exhibit focal mammary tumors at 100% penetrance. INT3 is a member of a family of genes, highly conserved through evolution and characterized by Drosophila melanogaster Notch and Caenorhabditis elegans lin-12, the function of which relates to cell fate determination. Upon transfection into the appropriate hosts, expression vectors of truncated Notch and lin-12, representing their respective cytoplasmic domains, have been demonstrated to effect their complete gene function with respect to cell fate determination. This suggests that the extracellular portion of these proteins function only to regulate activity. Reciprocal transplantation of transgenic FVB-3 and normal mammary tissue to the epithelium-divested fat pads of the respective donor females demonstrates that FVB-3 mammary epithelium is unable to grow and/or to functionally differentiate. However, normal epithelium grows and fully differentiates in transgenic FVB-3 fat pads, indicating that the dysfunction of FVB-3 mammary glands is due to a deficiency inherent in their epithelium. Electron microscopy reveals that transgenic INT3 epithelial cells do not form intercellular junctional complexes in the developing subadult mammary gland. The hormonal stimulation of pregnancy overcomes the deficiency for ductal growth so apparent in the virgin gland such that pregnant FVB-3 glands produce complete ductal systems. Nevertheless, during pregnancy, FVB-3 mammary cells fail to form secretory lobules and to produce milk. Examination of INT3 expression by immunocytochemistry and reverse transcriptase-PCR show that INT3 is expressed constitutively in mammary stroma and epithelia at all stages of postpubertal mammary evolution. These results indicate that deregulated expression of a truncated Int3 in mammary epithelial cells limits their capacity to perform the cell fate decisions required for morphogenesis and functional differentiation.


This article has been cited by other articles:


Home page
Physiol. Rev.Home page
C. Siebel and U. Lendahl
Notch Signaling in Development, Tissue Homeostasis, and Disease
Physiol Rev, October 1, 2017; 97(4): 1235 - 1294.
[Abstract] [Full Text] [PDF]


Home page
EMBO Rep.Home page
A. Santoro, T. Vlachou, M. Carminati, P. G. Pelicci, and M. Mapelli
Molecular mechanisms of asymmetric divisions in mammary stem cells
EMBO Rep., December 1, 2016; 17(12): 1700 - 1720.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. F. Schott, M. D. Landis, G. Dontu, K. A. Griffith, R. M. Layman, I. Krop, L. A. Paskett, H. Wong, L. E. Dobrolecki, M. T. Lewis, et al.
Preclinical and Clinical Studies of Gamma Secretase Inhibitors with Docetaxel on Human Breast Tumors
Clin. Cancer Res., March 15, 2013; 19(6): 1512 - 1524.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
Y. Sun, M. Klauzinska, R. J. Lake, J. M. Lee, S. Santopietro, A. Raafat, D. Salomon, R. Callahan, and S. Artavanis-Tsakonas
Trp53 regulates Notch 4 signaling through Mdm2
J. Cell Sci., April 1, 2011; 124(7): 1067 - 1076.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
M. Mazzone, L. M. Selfors, J. Albeck, M. Overholtzer, S. Sale, D. L. Carroll, D. Pandya, Y. Lu, G. B. Mills, J. C. Aster, et al.
Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells
PNAS, March 16, 2010; 107(11): 5012 - 5017.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
A. Klinakis, M. Szabolcs, K. Politi, H. Kiaris, S. Artavanis-Tsakonas, and A. Efstratiadis
Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice
PNAS, June 13, 2006; 103(24): 9262 - 9267.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
I. Swanson, B. A. Jude, A. R. Zhang, A. Pucker, Z. E. Smith, and T. V. Golovkina
Sequences within the gag Gene of Mouse Mammary Tumor Virus Needed for Mammary Gland Cell Transformation
J. Virol., April 1, 2006; 80(7): 3215 - 3224.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
K. G. Leong and A. Karsan
Recent insights into the role of Notch signaling in tumorigenesis
Blood, March 15, 2006; 107(6): 2223 - 2233.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
S. Stylianou, R. B. Clarke, and K. Brennan
Aberrant Activation of Notch Signaling in Human Breast Cancer
Cancer Res., February 1, 2006; 66(3): 1517 - 1525.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
M. Reedijk, S. Odorcic, L. Chang, H. Zhang, N. Miller, D. R. McCready, G. Lockwood, and S. E. Egan
High-level Coexpression of JAG1 and NOTCH1 Is Observed in Human Breast Cancer and Is Associated with Poor Overall Survival
Cancer Res., September 15, 2005; 65(18): 8530 - 8537.
[Abstract] [Full Text] [PDF]


Home page
J. Cell Sci.Home page
W. A. Woodward, M. S. Chen, F. Behbod, and J. M. Rosen
On mammary stem cells
J. Cell Sci., August 15, 2005; 118(16): 3585 - 3594.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
M. C. Stella, L. Trusolino, S. Pennacchietti, and P. M. Comoglio
Negative Feedback Regulation of Met-Dependent Invasive Growth by Notch
Mol. Cell. Biol., May 15, 2005; 25(10): 3982 - 3996.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
S. Jeffries, D. J. Robbins, and A. J. Capobianco
Characterization of a High-Molecular-Weight Notch Complex in the Nucleus of Notchic-Transformed RKE Cells and in a Human T-Cell Leukemia Cell Line
Mol. Cell. Biol., June 1, 2002; 22(11): 3927 - 3941.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
S. Jeffries and A. J. Capobianco
Neoplastic Transformation by Notch Requires Nuclear Localization
Mol. Cell. Biol., June 1, 2000; 20(11): 3928 - 3941.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
L. T. Krebs, Y. Xue, C. R. Norton, J. R. Shutter, M. Maguire, J. P. Sundberg, D. Gallahan, V. Closson, J. Kitajewski, R. Callahan, et al.
Notch signaling is essential for vascular morphogenesis in mice
Genes & Dev., June 1, 2000; 14(11): 1343 - 1352.
[Abstract] [Full Text]


Home page
DevelopmentHome page
M. Lin, C Leimeister, M Gessler, and R Kopan
Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers
Development, January 6, 2000; 127(11): 2421 - 2432.
[Abstract] [PDF]


Home page
DevelopmentHome page
H Uyttendaele, G Marazzi, G Wu, Q Yan, D Sassoon, and J Kitajewski
Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene
Development, July 1, 1996; 122(7): 2251 - 2259.
[Abstract] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1995 by the American Association of Cancer Research.