Cause of Failure of Lactation in Mouse Mammary Tumor Virus/Human Transforming Growth Factor   Transgenic Mice

1994 ◽  
Vol 205 (3) ◽  
pp. 236-242 ◽  
Author(s):  
S. Sakai ◽  
M. Mizuno ◽  
T. Harigaya ◽  
K. Yamamoto ◽  
T. Mori ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Transforming Growth Factor ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus ◽  
Cause Of Failure

scholarly journals Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice.

1996 ◽  
Vol 16 (10) ◽  
pp. 5726-5736 ◽  
Author(s):  
W J Muller ◽  
C L Arteaga ◽  
S K Muthuswamy ◽  
P M Siegel ◽  
M A Webster ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Transforming Growth Factor ◽  
Mammary Epithelium ◽  
Mammary Tumors ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Transgenic mice expressing either the neu proto-oncogene or transforming growth factor (TGF-alpha) in the mammary epithelium develop spontaneous focal mammary tumors that occur after a long latency. Since the epidermal growth factor receptor (EGFR) and Neu are capable of forming heterodimers that are responsive to EGFR ligands such as TGF-alpha, we examined whether coexpression of TGF-alpha and Neu in mammary epithelium could cooperate to accelerate the onset of mammary tumors. To test this hypothesis, we interbred separate transgenic strains harboring either a mouse mammary tumor virus/TGF-alpha or a mouse mammary tumor virus/neu transgene to generate bitransgenic mice that coexpress TGF-alpha and neu in the mammary epithelium. Female mice coexpressing TGF-alpha and neu developed multifocal mammary tumors which arose after a significantly shorter latency period than either parental strain alone. The development of these mammary tumors was correlated with the tyrosine phosphorylation of Neu and the recruitment of c-Src to the Neu complex. Immunoprecipitation and immunoblot analyses with EGFR- and Neu-specific antisera, however, failed to detect physical complexes of these two receptors. Taken together, these observations suggest that Neu and TGF-alpha cooperate in mammary tumorigenesis through a mechanism involving Neu and EGFR transactivation.

scholarly journals Transforming Growth Factor β Enhances the Glucocorticoid Response of the Mouse Mammary Tumor Virus Promoter through Smad and GA-Binding Proteins

2004 ◽  
Vol 78 (5) ◽  
pp. 2201-2211 ◽  
Author(s):  
Koldo Aurrekoetxea-Hernández ◽  
Elena Buetti
Keyword(s):  
Growth Factor ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Regulatory Elements ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

ABSTRACT Tissue-specific transcription is advantageously investigated by using viral promoters, which are selected for compact regulatory elements. Mouse mammary tumor virus (MMTV) has adapted to specialized cell types and targets initially B lymphocytes. We previously showed that, in B-cell lines, glucocorticoid-induced MMTV transcription requires an ETS family factor, GA-binding protein (GABP), bound in tandem to the MMTV DNA next to the glucocorticoid receptor (GR). We now report that transforming growth factor β (TGF-β) superinduces this response up to 10-fold through binding of its effectors, Smads, between the GABP-binding motifs. The basal level was unaffected. The TGF-β-glucocorticoid cooperation also depended on GR and GABP binding, was transferable to another promoter, and occurred both with transiently transfected and with integrated templates. Smad3 associated in vitro with GR, with GABPα (via the MH2 domain), and with GABPβ, Smad4 only with GABPα. Interactions of Smad3 with GABP (when coexpressed or endogenous to B cells) were shown by coprecipitation and by mammalian two-hybrid assay. This composite DNA element integrates three signaling pathways deriving from TGF-β, glucocorticoid hormones, and a unique ETS factor, and may allow MMTV to exploit factors from the milk. It may as well indicate novel possibilities for cellular regulatory networks.

Multiple regulatory domains in the mouse mammary tumor virus long terminal repeat revealed by analysis of fusion genes in transgenic mice

1988 ◽  
Vol 8 (1) ◽  
pp. 473-479
Author(s):  
T A Stewart ◽  
P G Hollingshead ◽  
S L Pitts
Keyword(s):  
Transgenic Mice ◽  
Long Terminal Repeat ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Terminal Repeat ◽  
Growth Hormone Gene ◽  
Fusion Genes ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Transcription initiated within the mouse mammary tumor virus (MTV) long terminal repeat (LTR) is regulated by glucocorticoids, androgens, and estrogen. However, expression of the virus in vivo and transcription of MTV LTR fusion genes in transgenic mice are not readily interpretable solely in terms of the influence of these hormones. To investigate whether there is a regulatory role for sequences within the LTR but outside the region known to be responsible for glucocorticoid induction, we have produced transgenic mice carrying genes in which various regions of the LTR have been linked to the human growth hormone gene. Analysis of expression of the fusion genes in these transgenic mice has demonstrated that the 5' end of the LTR can profoundly influence transcription initiated within the MTV LTR.

scholarly journals Transgenic mice carrying the mouse mammary tumor virus ras fusion gene: distinct effects in various tissues.

1989 ◽  
Vol 9 (2) ◽  
pp. 854-859 ◽  
Author(s):  
P J Tremblay ◽  
F Pothier ◽  
T Hoang ◽  
G Tremblay ◽  
S Brownstein ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Mammary Tumor ◽  
Lacrimal Gland ◽  
Mouse Mammary Tumor Virus ◽  
Fusion Gene ◽  
Ras Oncogene ◽  
Mammary Tumor Virus ◽  
Specific Effects ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

Transgenic mice carrying the v-Ha-ras oncogene under the control of the mouse mammary tumor virus long terminal repeat were produced. These mice exhibit several phenotypes: mammary tumors, bilateral hyperplasia of the harderian lacrimal gland, primary bronchio-alveolar lung adenocarcinoma, and splenomegaly. High levels of the transgene RNA were detected in mammary, harderian, and lung tumors. Accumulation of cells of the myeloid lineages was found in enlarged spleens. This phenotype may represent an indirect effect of v-Ha-ras expression on myeloid progenitors. Our data illustrate the cell-specific effects of v-Ha-ras.

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