Prolactin, epidermal growth factor or transforming growth factor-α activate a mammary cell-specific enhancer in mouse mammary tumor virus-long terminal repeat

1997 ◽  
Vol 129 (2) ◽  
pp. 145-155 ◽  
Author(s):  
S Haraguchi ◽  
R.A Good ◽  
R.W Engelman ◽  
S Greene ◽  
N.K Day
Keyword(s):  
Growth Factor ◽  
Mouse Mammary Tumor Virus ◽  
Transforming Growth Factor ◽  
Mammary Tumor Virus ◽  
Transforming Growth Factor Α ◽  
Mouse Mammary Tumor ◽  
Mammary Cell ◽  
Tumor Virus ◽  
Epidermal Growth ◽  
Factor Α

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.

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.

Inappropriate expression of human transforming growth factor (TGF)-α in the uterus of transgenic mouse causes downregulation of TGF-β receptors and delays the blastocyst-attachment reaction

1997 ◽  
Vol 18 (3) ◽  
pp. 243-257 ◽  
Author(s):  
S K Das ◽  
H Lim ◽  
J Wang ◽  
B C Paria ◽  
M BazDresch ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Receptor Subtypes ◽  
Transforming Growth Factor Α ◽  
Decidual Cells ◽  
Proliferation And Differentiation ◽  
Epidermal Growth ◽  
Β Receptor ◽  
Factor Α ◽  
Inappropriate Expression

ABSTRACT In the mouse, the initiation of the attachment reaction between the blastocyst trophectoderm and luminal epithelium of the receptive uterus occurs in the evening (2200-2300 h) of day 4 of pregnancy (day 1=vaginal plug) and is followed by proliferation and differentiation of stromal cells into decidual cells at the sites of blastocyst attachment. This investigation demonstrates that an inappropriate expression of the human transforming growth factor α (hTGF-α) transgene in the uterus under the direction of a mouse metallothionein-I promoter downregulates uterine expression of TGF-β receptor subtypes and delays the initiation of implantation (attachment reaction) resulting in delayed parturition. This delay in the attachment reaction is accompanied by deferred uterine expression of amphiregulin. The results suggest that a coordinated 'cross-talk' between the signaling pathways executed by epidermal growth factor-like growth factors and TGF-βs is important for the normal implantation process.

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