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GSE10290
Mus musculus
24 Downloadable Samples
Description
Beyond demonstrating a critical role for progesterone receptor signaling in normal mammary epithelial proliferation, the progesterone receptor knockout mouse disclosed the progesterone receptor along with its effector pathways as key determinants of mammary neoplastic progression. Despite these advances, however, further progress in our mechanistic understanding of progesterones involvement in mammary morphogenesis and tumorigenesis is contingent upon defining the essential effector pathways responsible for transducing the progesterone signal into a mammary proliferative and/or pro-survival response. Toward this goal, a judiciously chosen acute progesterone treatment regimen together with microarray methods was applied to the mammary gland of the normal mouse to uncover new effectors that operate immediately downstream of the progesterone mammary signal. Examination of the resultant progesterone-responsive transcriptome disclosed inhibitor of differentiation or DNA binding 4 (Id4) as a molecular target acutely induced by progesterone in the murine mammary epithelium.
Publication Title
Transcriptional response of the murine mammary gland to acute progesterone exposure.
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No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The small G-protein KRAS is crucial for mediating gonadotropin-induced events associated with ovulation. However, constitutive expression of KrasG12D in granulosa cells disrupted normal follicle development leading to the persistence of abnormal follicle-like structures containing non-mitotic cells. To determine what factors mediate this potent effect of KrasG12D, gene profiling analyses were done. We also analyzed KrasG12D;Cyp19-Cre and KrasG12D;Pgr-Cre mutant mouse models that express Cre prior to or after the initiation of granulosa cell differentiation, respectively. KrasG12D induced cell cycle arrest in granulosa cells of the KrasG12D;Cyp19-Cre mice but not in the KrasG12D;Pgr-Cre mice, documenting the cell context specific effect of KrasG12D. Expression of KrasG12D silenced the Kras gene, reduced cell cycle activator genes and impaired expression of granulosa cell and oocyte specific genes. Conversely, levels of PTEN and phosphorylated p38MAPK increased markedly in the mutant granulosa cells. Because disrupting Pten in granulosa cells leads to increased proliferation and survival, Pten was disrupted in the KrasG12D mutant mice. The Pten/Kras mutant mice were infertile but lacked GCTs. By contrast, the Ptenfl/fl;KrasG12D;Amhr2-Cre mice developed aggressive ovarian surface epithelial (OSE) cell tumors that did not occur in the Ptenfl/fl;KrasG12D;Cyp19-Cre or Ptenfl/fl;KrasG12D;Pgr-Cre mouse strains. These data document unequivocally that Amhr2-Cre is expressed in and mediates allelic recombination of oncogenic genes in OSE cells. That KrasG12D/Pten mutant granulosa cells do not transform but rather undergo cell cycle arrest indicates that they resist the oncogenic insults of Kras/Pten by robust self-protecting mechanisms that silence the Kras gene and elevate PTEN and phospho-p38MAPK.
Publication Title
Cell type-specific targeted mutations of Kras and Pten document proliferation arrest in granulosa cells versus oncogenic insult to ovarian surface epithelial cells.
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Age, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
Our previous study revealed that the basic helix-loop-helix transcription factor Hand2 is a downstream target of progesterone signaling in mouse uterine stroma at the time of implantation. Further, conditional deletion of Hand2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity.
Publication Title
The antiproliferative action of progesterone in uterine epithelium is mediated by Hand2.
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Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
Description
In order to gain a better understanding of Ihh action during embryo implantation, we constitutively activated Smo in the murine uterus using the PRcre mouse model (PRcre/+SmoM2+; SmoM2). Female SmoM2 mice were infertile. They exhibited normal serum progesterone levels and normal ovulation, but ova failed to be fertilized in vivo and the uterus failed to undergo the artificially induced decidual response. SmoM2 mice exhibited uterine hypertrophy. The endometrium had a reduced number of uterine glands and the endometrial stroma lost its normal morphologic characteristics. Microarray analysis of 3 month old SmoM2 uteri demonstrated a chondrocytic signature and confirmed that constitutive activation of SmoM2 increased extracellular matrix production. Thus, constitutive activation of Smo in the mouse uterus alters the extracellular matrix which interferes with early pregnancy.
Publication Title
Constitutive activation of smoothened leads to female infertility and altered uterine differentiation in the mouse.
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Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
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Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
Description
The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration.
Publication Title
A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
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Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Tumor associated macrophages are contributing to local invasion, angiogensis, and metastasis during the progression of many kinds of tumor including glioma
Publication Title
Oligodendrocyte progenitor cells promote neovascularization in glioma by disrupting the blood-brain barrier.
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Specimen part
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