CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential

Manzano, Ramón González; Montuenga, Luis M.; Dayton, Mark A.; Dent, Paul; Kinoshita, Ichiro; Vicent, Silvestre; Gardner, Ginger J.; Nguyen, Phuongmai; Choi, Yung Hyun; Trepel, Jane B.; Auersperg, Nelly; Birrer, Michael J.

doi:10.1038/sj.onc.1205542

Cited by 49 publications

(45 citation statements)

References 29 publications

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“…[19][20][21] Also, nuclear localization of DUSP1 has been reported in ovarian cancer as well as in fibroblasts, 22,23 whereas we did not detect any strong nuclear staining. All prostate carcinomas exhibited decreased expression compared to BPH, the basal cells of normal prostate or PIN, and in most of the cases, there was complete or almost complete lack of staining.…”

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confidence: 45%

“…In ovarian cancer cells, the reexpression decreased the malignant potential of the cells by inhibiting anchorage-dependent and -independent cell growth as well as cell motility. 22 Whereas, in pancreatic cancer cells, the downregulation decreased cell proliferation and tumorigenicity in nude mouse tumor model.…”

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confidence: 96%

“…In other carcinomas, such as colon, bladder and ovary, it has been shown that DUSP1 mRNA is expressed at relatively high levels in early stage tumors, whereas the expression decreases during tumor progression. 22,24 On the other hand, breast carcinomas seem to maintain relatively high expression of DUSP1 in all stages. 24,25 The data on experimental reexpression of DUSP1 in malignant cells have been controversial.…”

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confidence: 99%

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Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

Rauhala

Porkka

Tolonen

et al. 2005

Intl Journal of Cancer

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Inactivation of tumor suppressor genes through deletion, mutation and epigenetic silencing has been shown to occur in cancer. In our study, we combined DNA demethylation and histone deacetylation inhibition treatments with suppression subtraction hybridization (SSH) and cDNA microarrays to identify potentially epigenetically downregulated genes in PC-3 prostate cancer cell line. We found 11 genes whose expression was upregulated after relieving epigenetic regulation. Expression of 3 genes [dual-specificity phosphatase 1 (DUSP1), serum/glucocorticoid regulated kinase (SGK) and spermidine/spermine N1-acetyltransferase (SAT)] was subsequently studied in clinical sample material using real-time quantitative RT-PCR and immunohistochemistry. The DUSP1 and SGK mRNA expression was lower in hormone-refractory prostate carcinomas compared to benign prostate hyperplasia (BPH) or untreated prostate carcinomas. BPH, normal prostate and highgrade prostate intraepithelial neoplasia (PIN) expressed high levels of DUSP1 and SGK proteins. Ninety-two percent and 48% of the prostate carcinomas showed almost complete lack of DUSP1 and SGK proteins, respectively, indicating common downregulation of these genes. The genomic bisulphite sequencing did not reveal dense hypermethylation in the promoter regions of either DUSP1 or SGK. In conclusion, the data suggest that downregulation of DUSP1 and SGK is an early event and could be important in the tumorigenesis of prostate cancer. ' 2005 Wiley-Liss, Inc.

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Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

Rauhala

Porkka

Tolonen

et al. 2005

Intl Journal of Cancer

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“…(24,35,36). More recently, decreased expression of MKP-1 has been strongly associated with the advanced progression of human ovarian cancers (37). Yet, the regulatory mechanisms underlying sustained ERK1/2 activation and MKP-1 downregulation have not been well characterized.…”

Section: Exogenous Mkp-1 Phosphatase Activity Decreases Erk Phosphorymentioning

confidence: 99%

ERK1/2 Achieves Sustained Activation by Stimulating MAPK Phosphatase-1 Degradation via the Ubiquitin-Proteasome Pathway

Lin

Chuang

Yang

2003

Journal of Biological Chemistry

118

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Sustained extracellular signal-regulated kinase 1/2 (ERK1/2) activation does not always correlate with its upstream Ras-Raf-mitogen-activated protein kinase kinase 1/2 (MKK1/2) signal cascade in cancer cells, and the mechanism remains elusive. Here we report a novel mechanism by which sustained ERK1/2 activation is established. We demonstrate that Pb(II), a carcinogenic metal, persistently induces ERK1/2 activity in CL3 human lung cancer cells and that Ras-Raf-MKK1/2 signaling cannot fully account for such activation. It is intriguing that Pb(II) treatment reduces mitogenactivated protein kinase phosphatase 1 (MKP-1) protein levels in time-and dose-dependent manners, which correlates with sustained ERK1/2 activation, and that Pb(II) also induces mRNA and de novo protein synthesis of MKP-1. In Pb ( Members of the family of mitogen-activated protein kinase (MAPK) 1 proteins are vital intracellular signaling components that become phosphorylated and activated in response to a wide diversity of extracellular stimuli, including growth factors, cytokines, and environmental stresses (reviewed in Refs. 1-5). MAPKs are activated through a three-kinase module composed of a MAPK, a MAPK kinase (MKK), and a MKK kinase (MKKK). These MAPK modules are connected to cell surface receptors and activated via interaction with a family of small GTPases and MKKK kinases. Activated MAPKs phosphorylate many substrates, including cytoskeletal proteins, other kinases, phosphatases, enzymes, and transcription factors, thereby orchestrating several cellular alterations including proliferation, differentiation, survival, and apoptosis. The duration and strength of MAPK activation also affects these biological outcomes. Three major MAPK subfamilies have been extensively studied, i.e. the extracellular signal-regulated kinases (ERK1/2), the c-Jun N-terminal kinases (JNKs), and the p38 kinases. Activation of a particular MAPK signal must be controlled with high specificity and efficiency to achieve precise physiological regulation. The recent discovery of specific docking sites among the members of the MAPK cascades provide a mechanism that explains how specific and efficient signaling is established. For instance, a cluster of positively charged amino acids followed by an LXL motif called the D domain (or the kinase interaction motif, KIM) has been identified in MKKs, MAPK phosphatases (MKPs), and several MAPK substrates (6 -8). The D domain binds specifically to an acidic domain (common docking domain) within a docking groove of MAPKs (6 -8). Another docking site found in many ERK substrates is called the DEF motif (docking site for ERK, FXFP) (8, 9). These docking interactions facilitate phosphorylation of substrates by MAPKs on specific Ser or Thr residues followed by a Pro residue ((S/T)P sites).The small GTPase, MKKK, and MKK in the ERK pathway are known to be Ras, Raf, and MKK1/2, respectively (1-5). Activation of ERK1/2 requires a dual-phosphorylation by MKK1/2 on the Thr and Tyr residues of TEY sites within the activation loop, wherea...

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“…The level of DUSP1 was also investigated in human tumors. These initial studies revealed a higher DUSP1 expression in a range of human epithelial tumors including prostate, colon, and bladder, however, the expression of DUSP1 in tumors decreased progressively with a higher histological grade [15][16][17].Some studies also suggested that DUSP1 was involved in tumor therapy efficiency [18][19][20][21][22]. The function and mechanism of DUSP1 in tumors may be varied and complex.…”

Section: Introductionmentioning

confidence: 99%

Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

et al. 2016

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Dual-specificity phosphatase-1 (DUSP1/MKP1), as a member of the threoninetyrosine dual-specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1-mediated extracellular signalregulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine. It has been detected that DUSP1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. In various human cancers, abnormal expression of DUSP1 was observed which was associated with prognosis of tumor patients. Further studies have revealed its role in tumorigenesis and tumor progression. Besides, DUSP1 has been found to play a role in tumor chemotherapy, immunotherapy, and biotherapy. In this review, we will focus on the function and mechanism of DUSP1 in tumor cells and tumor treatment. Cancer Medicine Open Access 2062

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CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential

Cited by 49 publications

References 29 publications

Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

Dual‐specificity phosphatase 1 and serum/glucocorticoid‐regulated kinase are downregulated in prostate cancer

ERK1/2 Achieves Sustained Activation by Stimulating MAPK Phosphatase-1 Degradation via the Ubiquitin-Proteasome Pathway

Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

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