A global view of protein expression in human cells, tissues, and organs

Pontén, Fredrik; Gry, Marcus; Fagerberg, Linn; Lundberg, Emma; Asplund, Anna; Berglund, Lisa; Oksvold, Per; Björling, Erik; Hober, Sophia; Kampf, Caroline; Navani, Sanjay; Nilsson, Peter; Ottosson, Jenny; Persson, Anja Bondke; Wernérus, Henrik; Wester, Kenneth; Uhlén, Mathias

doi:10.1038/msb.2009.93

Cited by 187 publications

(157 citation statements)

References 32 publications

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“…Investigation of the mouse surface proteomes identified a large set of genes enriched in expression to the mouse trophoblast lineage. This was validated in human by a comparison to the Human Protein Atlas (13) where a 70% conservation of expression of one-to-one orthologs was observed in keeping with previous analyses (14). In addition, a detailed analysis of the endothelial and trophoblast proteomes highlighted the high degree of similarity of gene expression likely driven by their functional similarities.…”

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confidence: 65%

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Translational Analysis of Mouse and Human Placental Protein and mRNA Reveals Distinct Molecular Pathologies in Human Preeclampsia

Cox

Sharma

Evangelou

et al. 2011

Molecular & Cellular Proteomics

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Preeclampsia (PE) adversely impacts ϳ5% of pregnancies. Despite extensive research, no consistent biomarkers or cures have emerged, suggesting that different molecular mechanisms may cause clinically similar disease. To address this, we undertook a proteomics study with three main goals: (1) to identify a panel of cell surface markers that distinguish the trophoblast and endothelial cells of the placenta in the mouse; (2) to translate this marker set to human via the Human Protein Atlas database; and (3) to utilize the validated human trophoblast markers to identify subgroups of human preeclampsia. To achieve these goals, plasma membrane proteins at the blood tissue interfaces were extracted from placentas using intravascular silica-bead perfusion, and then identified using shotgun proteomics. We identified 1181 plasma membrane proteins, of which 171 were enriched at the maternal blood-trophoblast interface and 192 at the fetal endothelial interface with a 70% conservation of expression in humans. Three distinct molecular subgroups of human preeclampsia were identified in existing human microarray data by using expression patterns of trophoblast-enriched proteins. Analysis of all misexpressed genes revealed divergent dysfunctions including angiogenesis (subgroup 1), MAPK signaling (subgroup 2), and hormone biosynthesis and metabolism (subgroup 3). Subgroup 2 lacked expected changes in known preeclampsia markers (sFLT1, sENG) and uniquely overexpressed GNA12. In an independent set of 40 banked placental specimens, GNA12 was overexpressed during preeclampsia when co-incident with chronic hypertension. In the current study we used a novel translational analysis to integrate mouse and human trophoblast protein expression with human microarray data. This strategy identified distinct molecular pathologies in human preeclampsia. We conclude that clinically similar

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confidence: 65%

“…2A). We translated our mouse model findings to human biology using immunohistochemistry (IHC) available the Human Protein Atlas (13). As shown in Fig.…”

Section: Fig 2 Plasma Membrane Markers Of the Blood-tissue Interfacmentioning

confidence: 99%

Translational Analysis of Mouse and Human Placental Protein and mRNA Reveals Distinct Molecular Pathologies in Human Preeclampsia

Cox

Sharma

Evangelou

et al. 2011

Molecular & Cellular Proteomics

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“…31 The myeloma origin of the Karpas707 cell line was recently confirmed by performing comprehensive protein expression profiling in 48 human tissues and 45 human cell lines. 32 The HEK293T cells were cultured in DMEM medium (BioWhittaker) with the same supplements as mentioned before. …”

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confidence: 99%

IGF-1 suppresses Bim expression in multiple myeloma via epigenetic and posttranslational mechanisms

Bruyne

Bos

Schuit

et al. 2010

Blood

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IntroductionMultiple myeloma (MM) is a lethal plasma cell malignancy hallmarked by uncontrolled accumulation of monoclonal plasma cells in the bone marrow (BM). 1 There, the MM cells receive signals to survive and proliferate because of the existence of functional, mutual interactions through growth factors and adhesion molecules. 2 Importantly, these interactions also confer resistance to conventional therapies. 2 One of the most important growth factors involved in MM progression is insulin-like growth factor-1 (IGF-1). [3][4][5] This cytokine induces proliferation of both interleukin-6 (IL-6)-independent and -dependent cell lines, acts synergistically with IL-6, and protects MM cells from dexamethasone-induced apoptosis. 3 Moreover, IGF-1 also stimulates homing and production of angiogenic factors. 4,6,7 Binding to its receptor results in the activation of the Ras/Raf/MAPK (mitogen-activated protein kinase)/Erk (mainly triggering proliferation and secretion of vascular endothelial growth factor) and the PI-3K (phosphatidylinositol-3 kinase)/Akt pathways (involved mainly in antiapoptotic stimuli and mediating migration). 6,8 Both IGF-1 serum levels and IGF-1 receptor (IGF-1R) expression by the MM cells are important negative prognostic factors in MM. 9,10 The central role of IGF-1 in the MM pathophysiology is further supported by the encouraging preclinical results observed after targeting the IGF-1R with neutralizing antibodies or small molecule inhibitors. Previously, we demonstrated the efficacy of the IGF-1R tyrosine kinase inhibitor picropodophyllin to block the function of IGF-1R in vitro and in vivo and this both in murine and human MM cells. 11,12 The anti-MM activity of selective IGF-1R inhibitors was also confirmed with the use of the selective kinase inhibitor NVP-ADW742 in an orthotopic xenograft MM model. 4 Clinical trials examining the effect of both blocking antibodies and small molecule inhibitors are currently ongoing. 3 Bim (Bcl2like11) is a member of the BH3-only group of the Bcl-2 protein family and is a mediator of apoptosis. 13,14 Bim is a sensor of cell stress (withdrawal or inhibition of growth factor signaling or treatment with numerous cytotoxic agents) 13,15 and promotes apoptosis either indirectly by antagonizing the inhibitory function of the Bcl-2/Bcl-Xl members and thus liberating the innate cytotoxic Bax-like members or directly by activating the Bax-like members. 13 Three major isoforms of Bim are known: extra-long (BimEL), long (BimL), and short (BimS). All 3 isoforms induce apoptosis; the shortest being the most potent but the longest the most preponderant. 16 The proapoptotic activity of Bim seems to be controlled in various ways. In healthy cells, Bim is sequestered in its inactive form to the microtubular cytoskeleton or exists as inactive heterodimers (with antiapoptotic Bcl-2 family members) sequestered to the mitochondria. 17 In B and MM cells, Bim appears to be constitutively associated with Mcl-1. At induction of apoptosis, Bim is released from Mcl-1, thus activating ...

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“…Both staining patterns have been previously observed. 42,45 Despite a correlation between nuclear and cytoplasmic staining, we expect CIP2A to have distinct roles in the different cellular compartments. Cytoplasmic CIP2A is available for PP2A regulation and therefore subsequent MYC activation, while nuclear CIP2A might be involved in transcription regulation or is transported into the nucleus while in complex with other protein subunits.…”

Section: Discussionmentioning

confidence: 99%

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

et al. 2017

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CIP2A is emerging as an oncoprotein overexpressed commonly across many tumours and generally correlated with higher tumour grade and therapeutic resistance. CIP2A drives an oncogenic potential through inhibiting protein phosphatase 2A, stabilizing MYC, and promoting epithelial-to-mesenchymal transition, although further biological mechanisms for CIP2A are yet to be defined. CIP2A protein expression was studied by immunohistochemistry in oestrogen receptor-positive primary breast cancers (n = 250) obtained from the Leeds Tissue Bank. In total, 51 cases presented with a relapse or metastasis during adjuvant treatment with tamoxifen and were regarded as tamoxifen resistant. CIP2A expression was scored separately for cytoplasmic, nuclear, or membranous staining, and scores were tested for statistically significant relationships with clinicopathological features. Membranous CIP2A was preferentially expressed in cases who experienced a recurrence during tamoxifen treatment thus predicting a worse overall survival (log rank = 8.357, p = 0.004) and disease-free survival (log rank = 21.766, p < 0.001). Cox multivariate analysis indicates that it is an independent prognostic indicator for overall survival (hazard ratio = 4.310, p = 0.013) and disease-free survival (hazard ratio = 5.449, p = 0.002). In this study, we propose the assessment of membranous CIP2A expression as a potential novel prognostic and predictive indicator for tamoxifen resistance and recurrence within oestrogen receptor-positive breast cancer.

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A global view of protein expression in human cells, tissues, and organs

Cited by 187 publications

References 32 publications

Translational Analysis of Mouse and Human Placental Protein and mRNA Reveals Distinct Molecular Pathologies in Human Preeclampsia

Translational Analysis of Mouse and Human Placental Protein and mRNA Reveals Distinct Molecular Pathologies in Human Preeclampsia

IGF-1 suppresses Bim expression in multiple myeloma via epigenetic and posttranslational mechanisms

CIP2A expression predicts recurrences of tamoxifen-treated breast cancer

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