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Analysis of Gene Expression in PTHrP-/- Mammary Buds

ABSTRACT: Analysis of Gene Expression in PTHrP-/- Mammary Buds Supports a Role for BMP Signaling and MMP2 in the Initiation of Ductal Morphogenesis. Parathyroid hormone-related protein (PTHrP) acts on the mammary mesenchyme and is required for proper embryonic mammary development. In order to understand PTHrP’s effects on mesenchymal cells, we profiled gene expression in WT and PTHrP-/- mammary buds, and in WT and K14-PTHrP ventral skin, at E15.5. By cross-referencing the differences in gene expression between these groups, we identified 35 genes potentially regulated by PTHrP in the mammary mesenchyme, including 6 genes known to be involved in BMP signaling. One of these genes was MMP2. We demonstrated that PTHrP and BMP4 regulate MMP2 gene expression and MMP2 activity in mesenchymal cells. Using mammary bud cultures, we demonstrated that MMP2 acts downstream of PTHrP to stimulate ductal outgrowth. Future studies on the functional role of other genes on this list should expand our knowledge of how PTHrP signaling triggers the onset of ductal outgrowth from the embryonic mammary buds.

ORGANISM(S): Mus musculus

PROVIDER: GSE17654 | GEO | 2009/08/15

SECONDARY ACCESSION(S): PRJNA118605

REPOSITORIES: GEO

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Analysis of Gene Expression in PTHrP-/- Mammary Buds

Project description:Analysis of Gene Expression in PTHrP-/- Mammary Buds Supports a Role for BMP Signaling and MMP2 in the Initiation of Ductal Morphogenesis. Parathyroid hormone-related protein (PTHrP) acts on the mammary mesenchyme and is required for proper embryonic mammary development. In order to understand PTHrP’s effects on mesenchymal cells, we profiled gene expression in WT and PTHrP-/- mammary buds, and in WT and K14-PTHrP ventral skin, at E15.5. By cross-referencing the differences in gene expression between these groups, we identified 35 genes potentially regulated by PTHrP in the mammary mesenchyme, including 6 genes known to be involved in BMP signaling. One of these genes was MMP2. We demonstrated that PTHrP and BMP4 regulate MMP2 gene expression and MMP2 activity in mesenchymal cells. Using mammary bud cultures, we demonstrated that MMP2 acts downstream of PTHrP to stimulate ductal outgrowth. Future studies on the functional role of other genes on this list should expand our knowledge of how PTHrP signaling triggers the onset of ductal outgrowth from the embryonic mammary buds. Five experimental groups (WT mammary buds, PTHrP-/- mammary buds, WT ventral skin, K14WT ventral skin, K14-PTHrP ventral skin). Three replicates in each group. Differentially expressed genes are listed in the following supplementary files: GSE17654_List1a-Higher_in_KO_Buds_than_WT_Buds.txt GSE17654_List1b-Lower_in_KO_Buds_than_WT_Buds.txt GSE17654_List2a-Higher_in_WT_Skin_than_WT_Buds.txt GSE17654_List2b-Lower_in_WT_Skin_than_WT_Buds.txt

2009-08-15 | E-GEOD-17654 | biostudies-arrayexpress

Comparative bulk RNAseq analysis of Control and PTH/PTHrP recepter-deficient PTHrP+ dental follicle cells

Project description:Lack of PTH/PTHrP receptor in PTHrP+ dental follicle cells causes a cell fate shift and premature differentiation. Here, we set out to reveal the transcriptome change induced by deficiency in PTH/PTHrP receptor in PTHrP+ dental follicle cells

2018-08-01 | GSE117936 | GEO

PTHrP overexpression in MCF7 cells

Project description:A PTHrP construct expressing full-length secreted PTHrP (-36-139aa) was stably expressed in MCF7 cells. The goal of the study was to determine the gene targets of PTHrP in human MCF7 breast cancer cells.

2018-05-30 | GSE110713 | GEO

PTH and PTHrP treatment of primary adipocytes

Project description:Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are involved in cachexia associated with chronic kidney disease and cancer respectively. Tumor-derived PTHrP triggers adipose tissue browning and thereby leads to wasting of fat tissue in tumor-bearing mice. Similarly, elevated in 5/6 nephrectomized mice, PTH stimulates adipose tissue browning and wasting. Mice lacking the PTH/PTHrP receptor in their fat tissue are resistant to wasting of both adipose tissue and skeletal muscle. Therefore, the PTH/PTHrP signaling in adipocytes should activate various pathways that contribute to hypermetabolism and muscle wasting.

2015-12-01 | GSE74082 | GEO

CrkII transgene induces atypical mammary gland development and tumorigenesis

Project description:The v-Crk protein was originally isolated as the oncogene fusion product of the CT10 chicken retrovirus. Cellular homologues of v-Crk include Crk, which encodes two alternatively spliced proteins (CrkI and CrkII), and CrkL. Though CrkI/II proteins are elevated in several types of cancer, including breast, the question of whether these Crk adaptor proteins can promote breast cancer has not been addressed. We created a transgenic mouse model that allows the expression of CrkII through the hormonally responsive mouse mammary tumor virus promoter. During puberty, transgenic mice were found to have delayed ductal outgrowth, characterized by increased collagen surrounding the terminal end buds. In post-pubertal mice, precocious ductal branching was observed and associated with increased proliferation. Focal mammary tumors appeared in a subset of animals, with a latency of approximately 15 months. Mouse mammary tumor virus/CrkII tumors showed high levels of Crk protein as well as various cytokeratin markers characteristic of their respective tumor pathologies. This study demonstrates that the precise expression of CrkII is critical for integrating signals for ductal outgrowth and branching morphogenesis during mammary gland development. Furthermore, this study provides evidence for a potential role of CrkII in integrating signals for breast cancer progression in vivo, which has important implications for elevated CrkII observed in human cancer. Two T47D-CrkII samples vs two T47D samples.

2011-07-17 | E-GEOD-30731 | biostudies-arrayexpress

Mus musculus

Project description:Analysis of Gene Expression in PTHrP-/- Mammary Buds

| PRJNA118605 | ENA

PTHrP-responsive genes in breast cancer

Project description:Parathyroid hormone-related protein (PTHrP) is overexpressed in many cancer types. This secretory protein can induce hypercalcaemia of malignancy by mimicking the action of calcium-regulating parathyroid hormone (PTH). PTHrP may also be involved in the regulation of migration, invasion, proliferation and apoptosis. It can either stimulate signal cascades, such as the cAMP pathway, or act on not yet defined targets in the nucleus. In this study, we analyzed the effect of PTHrP-specific siRNA on gene expression in MDA-MB-231 breast cancer cells. MDA-MB-231 cells were either transfected with the PTHrP-specific siRNA (siPTHrP) or a control siRNA (siLuc). Differences in gene expression pattern in siPTHrP- vs. siLuc-treated cells were measured by microarray analysis. More than 200 differentially expressed genes were found. Some of these genes have important functions in carcinogenesis. Keywords: siRNA knock-down analysis

2006-02-25 | GSE4292 | GEO

Single cell RNAseq analysis of PTHrP+ dental follicle cells

Project description:PTHrP is abundantly expressed by dental follicle cells. We set out to reveal single cell profiles of FACS-sorted PTHrP-mCherry+ cells isolated from the mandible.

2018-09-19 | GSE120108 | GEO

Pubertal Ductal Morphogenesis: Isolation and Transcriptome Analysis of the Terminal End Bud.

Project description:The terminal end buds (TEB) are the growing part of the ductal mammary epithelium during puberty, which enable the formation of the primary mammary epithelial network. These bulbous end structures are highly proliferative, and this allows the ductal expansion into the mammary fat pad. The TEB comprise of an outer cap cell layer, which include the progenitor cells of the myoepithelium, and the body cells, which are thought to be the progenitors from which the luminal epithelium is formed. Since TEBs make up only a minute part of the whole mammary tissue, associated factors can be easily missed in whole-tissue section analysis. We have therefore optimised a method to enzymatically separate TEB and ducts, respectively, from the surrounding stroma of pubertal mice and performed transcriptome analysis on the isolated structures to identify potential novel regulators of epithelial outgrowth.

2017-02-02 | GSE94371 | GEO

CrkII transgene induces atypical mammary gland development and tumorigenesis

2011-07-18 | GSE30731 | GEO

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