Knocking Off SOCS Genes in the Mammary Gland

Sutherland, Kate D.; Lindeman, Geoffrey J.; Visvader, Jane E.

doi:10.4161/cc.6.7.4037

Cited by 44 publications

(36 citation statements)

References 45 publications

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“…2A). In addition to the above mRNAs, the levels of mRNA encoding the PRLR, which has a well described role in b cells during pregnancy, as well as suppressor of cytokine signaling 2, which is known to attenuate PRLR signaling (Sutherland et al 2007), were also increased by pregnancy in the global expression analysis and confirmed in real-time RT-PCR studies.…”

Section: Global Rna Expression Analysis Of Mouse Islets During Pregnancymentioning

confidence: 82%

Regulation of pancreatic islet gene expression in mouse islets by pregnancy

Layden

Durai²,

Newman³

et al. 2010

Journal of Endocrinology

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Pancreatic b cells adapt to pregnancy-induced insulin resistance by unclear mechanisms. This study sought to identify genes involved in b cell adaptation during pregnancy. To examine changes in global RNA expression during pregnancy, murine islets were isolated at a time point of increased b cell proliferation (E13 . 5), and RNA levels were determined by two different assays (global gene expression array and G-protein-coupled receptor (GPCR) array). Follow-up studies confirmed the findings for select genes. Differential expression of 110 genes was identified and follow-up studies confirmed the changes in select genes at both the RNA and protein level. Surfactant protein D (SP-D) mRNA and protein levels exhibited large increases, which were confirmed in murine islets. Cytokine-induced expression of SP-D in islets was also demonstrated, suggesting a possible role as an anti-inflammatory molecule. Complementing these studies, an expression array was performed to define pregnancy-induced changes in expression of GPCRs that are known to impact islet cell function and proliferation. This assay, the results of which were confirmed using realtime reverse transcription-PCR assays, demonstrated that free fatty acid receptor 2 and cholecystokinin receptor A mRNA levels were increased at E13 . 5. This study has identified multiple novel targets that may be important for the adaptation of islets to pregnancy.

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Section: Global Rna Expression Analysis Of Mouse Islets During Pregnancymentioning

confidence: 82%

Regulation of pancreatic islet gene expression in mouse islets by pregnancy

Layden

Durai²,

Newman³

et al. 2010

Journal of Endocrinology

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“…In mammary gland development, SOCS-3 is essential for cell survival. Sutherland and colleagues could prove that silencing of the SOCS-3 gene leads to accelerated apoptosis through activation of STAT3 and induction of proapoptotic Bak and Bax proteins (46,47). In many tumors, SOCS-3 is silenced through gene promoter hypermethylation.…”

Section: Cancer Researchmentioning

confidence: 99%

Down-regulation of Suppressor of Cytokine Signaling-3 Causes Prostate Cancer Cell Death through Activation of the Extrinsic and Intrinsic Apoptosis Pathways

et al. 2009

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Suppressor of cytokine signaling-3 (SOCS-3) acts as a negative feedback regulator of the Janus-activated kinase/ signal transducers and activators of transcription factors signaling pathway and plays an important role in the development and progression of various cancers. To better understand the role of SOCS-3 in prostate cancer, SOCS-3 expression was down-regulated in DU-145, LNCaP-IL-6+, and PC3 cells by consecutive SOCS-3 small interfering RNA transfections. SOCS-3 mRNA and protein expression as measured by quantitative reverse transcription-PCR and Western blot, respectively, were decreased by f70% to 80% compared with controls. We observed a significant decrease in cell proliferation and viability in all SOCS-3-positive cell lines but not in the parental LNCaP cell line, which is SOCS-3 negative. In this study, we show that down-regulation of SOCS-3 leads to an increased cell death in prostate cancer cell lines. We found a considerable increase in the activation of the proapoptotic caspase-3/caspase-7, caspase-8, and caspase-9. A significant up-regulation of cleaved poly(ADPribose) polymerase and inhibition of Bcl-2 expression was observed in all SOCS-3-positive cell lines. Overexpression of Bcl-2 could rescue cells with decreased SOCS-3 levels from going into apoptosis. Tissue microarray data prove that SOCS-3 is highly expressed in castration-refractory tumor samples. In conclusion, we show that SOCS-3 is an important protein in the survival machinery in prostate cancer and is overexpressed in castration-resistant tumors. SOCS-3 knockdown results in an increase of cell death via activation of the extrinsic and intrinsic apoptosis pathways.

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“…STAT1 and STAT3 proteins may also be involved in Prl signaling with nuclear translocation of their homo-and heterodimers. SOCS1, 2, and 3 attenuate Prl signaling [47,48,[51][52][53] .…”

Section: Prolactin Signalingmentioning

confidence: 99%

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

Smirnova¹

2007

WJG

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The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes, cholangiocarcinoma predisposition and development. Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.

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Knocking Off SOCS Genes in the Mammary Gland

Cited by 44 publications

References 45 publications

Regulation of pancreatic islet gene expression in mouse islets by pregnancy

Regulation of pancreatic islet gene expression in mouse islets by pregnancy

Down-regulation of Suppressor of Cytokine Signaling-3 Causes Prostate Cancer Cell Death through Activation of the Extrinsic and Intrinsic Apoptosis Pathways

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

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