PTHrP Induces STAT5 Activation, Secretory Differentiation and Mammary Tumor Progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Martin Garcia Sola E
PROVIDER: E-MTAB-11281 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:With the aim of identifying new pathways and genes regulated by PTH(1-34) and PTH-related protein 1-141 [PTHrP(1-141)] in osteoblasts, this study was carried out using a mouse marrow stromal cell line, Kusa 4b10, that acquires features of the osteoblastic phenotype in long-term culture conditions. After the appearance of functional PTH receptor 1 (PTHR1) in Kusa 4b10 cells, they were treated with either PTH(1-34) or PTHrP(1-141), and RNA was subjected to Affymetrix whole mouse genome array. Timecourse experiment on Kusa4b10 cell lines, treatment with PTH or PTHrP, collection at 1, 6 and 24 hours NOTE: This work has been published in 2008 (PMID 18627264); Since the original normalised data for this project is unavailable, the data has been re-normalised using a standard method for GEO submission in 2013. Therefore, the re-normalized data represented in this records may differ slightly from the original normalized data in the publication.
2013-04-10 | E-GEOD-45895 | biostudies-arrayexpress
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
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
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
Project description:The 5-year survival rate for women with metastatic breast cancer is 29%. Potential biomarkers identification is important for new therapeutic treatment in affected patients. Previous studies have shown that Parathyroid hormone-related peptide (PTHrP) plays a critical role in breast cancer growth and metastasis. The aim of our study was to use a genetically modified breast cancer mouse model to precisely examine the role of PTHrP from early primary breast cancer initiation to late progression. We identified a novel lncRNA, a new target for fatty acid metabolism that can be regulated by PTHrP in our unique mouse breast cancer model. We confirmed that a potential human lncRNA, OLMALINC, plays a similar role in fatty acid metabolism that can be regulated by PTHrP. Therefore, we validated our mouse finding in the human breast cancer cell lines. Genetically engineered mouse models provide valuable tools to study the molecular progression for breast cancer metastasis.
2023-12-30 | GSE225877 | GEO
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.
2009-08-15 | GSE17654 | GEO
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
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
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
Project description:Prolonged skeletal unloading through bedrest results in bone loss similar to that observed in elderly osteoporotic patients, but with an accelerated timeframe. This rapid effect on weight-bearing bones is also observed in astronauts who lose up to 2% of their bone mass per month spent in Space. Despite important implications for Spaceflight travellers and bedridden patients on Earth, the exact mechanisms involved in disuse osteoporosis have not been elucidated. Parathyroid hormone-related protein (PTHrP) regulates many physiological processes including skeletal development, and has been proposed as a gravisensor. To investigate the role of PTHrP in microgravity-induced bone loss, trabecular osteoblasts (TOs) from Pthrp+/+ and -/- mice were exposed to simulated microgravity for 6 days. Viability of TOs decreased in inverse proportion to PTHrP expression levels. Microarray analysis of Pthrp+/+ TOs after 6 days at 0g revealed expression changes in genes encoding prolactins,apoptosis and survival molecules, bone metabolism and extra-cellular matrix composition proteins, chemokines, IGF family and Wnt-related signalling molecules. Importantly, 88% of 0g-induced expression changes in Pthrp+/+ cells overlap those observed in Pthrp-/- cells in normal gravity. Pulsatile treatment with PTHrP1-36 peptide during microgravity exposure reversed a large proportion of 0g-induced changes in Pthrp+/+ TOs. Our results confirm PTHrP efficacy as an anabolic agent to prevent microgravity-induced cell death in TOs. Total RNA samples extracted from Pthrp+/+and -/- trabecular osteoblasts (TOs) exposed for 6 days to simulated 0g in Synthecon rotating cell, or left 6 days in culture at 1g. Cells had either been treated with a pulsatile treatment (2 h/day) of PTHrP1-36 peptide (10-8M) or received a change in growth medium. In total: 8 different conditions with 2 replicates each, i.e. Pthrp+/+ TOs at 0g or 1g with or without PTHrP1-36 treatment, and Pthrp-/- TOs at 0g or 1 g,with or without PTHrP1-36 treatment.
2016-08-09 | E-GEOD-78980 | biostudies-arrayexpress