Effect of SOCS2 R96C mutation on mouse mammary gland development and function
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE225441 | GEO | 2024/02/26
REPOSITORIES: GEO
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Project description:SOCS2 Ensures Metabolic Function and Mass Restoration During Liver Regeneration - SOCS2 plays distinct and contrasting roles during liver regeneration. Early after injury, SOCS2 expression increases and limits the rate of regeneration, preserving metabolic activity. Surprisingly, at later times, the role of SOCS2 reverses to promote liver regeneration by stimulating GH release from the pituitary via effects on serum levels of insulin-like growth factor 1. Loss of SOCS2 promotes GH signaling by increasing growth hormone receptor levels and driving phosphorylation of proteins in the GH pathway, establishing a state of hyper-responsiveness to GH. These findings suggest a single protein can play contrasting roles at different times after liver injury and modulation of GH signaling achieves an optimal rate of liver regeneration to balance metabolic and restorative needs. To further understand the mechanism by which SOCS2 increases early liver regeneration, we performed microarray analysis of Socs2-null mice wildtype mice at 24 and 36 hours after hepatectomy.
2014-02-01 | GSE51801 | GEO
Project description:SOCS2 Ensures Metabolic Function and Mass Restoration During Liver Regeneration - SOCS2 plays distinct and contrasting roles during liver regeneration. Early after injury, SOCS2 expression increases and limits the rate of regeneration, preserving metabolic activity. Surprisingly, at later times, the role of SOCS2 reverses to promote liver regeneration by stimulating GH release from the pituitary via effects on serum levels of insulin-like growth factor 1. Loss of SOCS2 promotes GH signaling by increasing growth hormone receptor levels and driving phosphorylation of proteins in the GH pathway, establishing a state of hyper-responsiveness to GH. These findings suggest a single protein can play contrasting roles at different times after liver injury and modulation of GH signaling achieves an optimal rate of liver regeneration to balance metabolic and restorative needs. To further understand the mechanism by which SOCS2 increases early liver regeneration, we performed microarray analysis of Socs2-null mice wildtype mice at 24 and 36 hours after hepatectomy. C57BL/6 mice where used as wildtype controls. Socs2-null animals were maintained on a C57BL/6 background. Both wildtype and Socs2-null adult mice were subjected to 2/3 hepatectomy and liver tissue isolated at 24 hours and 36 hours post hepatectomy. Time zero was without hepatectomy in age-matched mice for each genotype. Total RNA isolated from collected liver tissues was pooled for three animals at each time point and two biological replicates (3 pooled liver RNAs each) were labeled for array analysis. This results in a total of 12 microarrays.
2014-02-01 | E-GEOD-51801 | biostudies-arrayexpress
Project description:Hematopoietic stem cells (HSC) promptly adapt hematopoiesis to stress conditions, such as infection and cancer, by replenishing bone marrow (BM)-derived circulating populations while preserving the stem cell reservoir. SOCS2, a feedback inhibitor of JAK/STAT pathways is expressed in most primitive HSC and is upregulated in response to STAT5-inducing cytokines. We demonstrate that Socs2 deficiency unleashes HSC proliferation in vitro sustaining STAT5 phosphorylation in response to the hematopoietic cytokines IL-3, thrombopoietin (TPO) and GM-CSF. In vivo, SOCS2 deficiency leads to unrestricted myelopoietic response to 5-fluorouracil and, in turn, induces exhaustion of long-term HSC function along serial BM transplantations. These findings unveiled a new regulatory role for SOCS2 in normalizing HSC functions under hematopoietic stress and prompted its investigation for involvement in malignant hematopoiesis. Indeed, in acute myeloid and lymphoblastic leukemias high levels of SOCS2 characterize unfavorable subclasses with MLL and BCR/ABL abnormalities. Analysis of gene expression profiles showed that high SOCS2 positively correlates with a pool of genes that are significatively enriched of members of the stemness signature described in acute myeloid leukemia. Unexpectedly, in acute leukemias, SOCS2 and its related genes are not controlled by STAT5 signaling, they are rather part of regulatory networks fronted by IKZF1/Ikaros and MEF2C, two key hematopoietic stemness-related transcriptional factors that, independently, have been described in leukemias but never linked together in controlling SOCS2 expression and unfavorable leukemia outcome.
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Project description:Deregulation of cytokine- and growth factor signaling due to altered expression of endogenous regulators is well recognized in prostate and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of growth hormone, IGF and prolactin signaling, that have been implicated in carcinogenesis. In this study we elucidate expression pattern and functional significance of SOCS2 in prostate cancer (PCa). Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed significantly enhanced expression in tumor compared to benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited prostate cancer cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we prove for the first time that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with androgen receptor expression in malignant tissue of patients. Taken together, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo.
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Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. We identified a novel androgen-regulated long non-coding (lnc) RNA, SOCS2-AS1. In order to investigate the SOCS2-AS1 function in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines (LNCaP and LTAD) after siSOCS2-AS1 or siSOCS2 treatment. We also treated cells with vehicle or androgen to analyzed the effects of siSOCS2-AS1 on AR function. Observation of androgen dependent gene expression changes after treatmet with siSOCS2-AS1 with microarray.
2016-08-01 | E-GEOD-82224 | biostudies-arrayexpress
Project description:Deregulation of cytokine- and growth factor signaling due to altered expression of endogenous regulators is well recognized in prostate and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of growth hormone, IGF and prolactin signaling, that have been implicated in carcinogenesis. In this study we elucidate expression pattern and functional significance of SOCS2 in prostate cancer (PCa). Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed significantly enhanced expression in tumor compared to benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited prostate cancer cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we prove for the first time that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with androgen receptor expression in malignant tissue of patients. Taken together, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo. Prostate cancer cell lines LNCaP, DUCaP and VCaP cells were cultured in the absence or presence of R1881, an androgen in three independent experiments. Differential gene expression was determined by comparing R1881 treated samples with the corresponding controls (EtOH treated samples).
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2016-08-01 | GSE82224 | GEO
Project description:In this study, the profile of mastitis-induced differential gene expression in the mammary tissue of Chinese Holstein cattle was investigated by Gene-Chip microarray and bioinformatics Our experiments included RNA samples was isolated from the mammary tissue of adult Chinese Holstein cows during late lactation with (n=3) and without (n=3) mastitis
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Project description:Ovine mastitis is defined as the inflammation of the sheep udder, most commonly caused in response to intramammary infections. Based on the occurrence of clinical signs, mastitis is characterized as either clinical or subclinical (SCM). The impact of ovine SCM on the overall sustainability of dairy sheep farms has been documented underpinning the significance of efficient diagnosis. Although SCM can be detected in cows, the performance and the validity of the methods used do not transfer in dairy sheep. This fact challenges the development of evidence-based ovine udder health management protocols and renders the detection and control of ovine mastitis rather problematic. Currently, cell culture-based models are being successfully used in biomedical studies and have also been effectively used in the case of bovine mastitis. The objective of the present study was to culture ovine primary mammary cells for the development of 2D and 3D cell culture-based models for the study of ovine SCM. Cells were infected by mastitis-inducing pathogens mimicking the pathogenesis of SCM as derived by natural intramammary infections. The secreted proteins were subjected to mass-spectrometry resulting in the identification of 79 distinct proteins. Among those, several had already been identified in healthy or mastitic milk, while others were detected for the first time in the ovine mammary secretome. The development of cell-based models for the early detection and the overall study of SCM has the potential to be applicable and beneficial for the udder health management in dairy sheep.
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