Selective Activation of Ceruloplasmin Promoter in Ovarian Tumors

Lee, Christine M.; Lo, Hui-Wen; Shao, Ru; Wang, Shao‐Chun; Xia, Weiya; Gershenson, David M.; Hung, Mien‐Chie

doi:10.1158/0008-5472.can-03-2551

Cited by 36 publications

(32 citation statements)

References 21 publications

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“…pRL-TK (Promega) was cotransfected as a control for transfection efficiency. After transfection and experiment treatments, cells were lysed and luciferase activity was measured using Dual Luciferase kit (Promega) according to manufacturer's instructions (27,28).…”

Section: Methodsmentioning

confidence: 99%

Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-regulation of TWIST Gene Expression

et al. 2007

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Aberrant epidermal growth factor receptor (EGFR) signaling is a major cause of tumor progression and metastasis; the underlying mechanisms, however, are not well understood. In particular, it remains elusive whether deregulated EGFR pathway is involved in epithelial-mesenchymal transition (EMT), an early event that occurs during metastasis of cancers of an epithelial origin. Here, we show that EGF induces EGFRexpressing cancer cells to undergo a transition from the epithelial to the spindle-like mesenchymal morphology. EGF reduced E-cadherin expression and increased that of mesenchymal proteins. In search of a downstream mediator that may account for EGF-induced EMT, we focused on transcription repressors of E-cadherin, TWIST, SLUG, and Snail and found that cancer cells express high levels of TWIST and that EGF enhances its expression. EGF significantly increases TWIST transcripts and protein in EGFR-expressing lines. Forced expression of EGFR reactivates TWIST expression in EGFR-null cells. TWIST expression is suppressed by EGFR and Janusactivated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) inhibitors, but not significantly by those targeting phosphoinositide-3 kinase and MEK/ERK. Furthermore, constitutively active STAT3 significantly activates the TWIST promoter, whereas the JAK/STAT3 inhibitor and dominant-negative STAT3 suppressed TWIST promoter. Deletion/mutation studies further show that a 26-bp promoter region contains putative STAT3 elements required for the EGFresponsiveness of the TWIST promoter. Chromatin immunoprecipitation assays further show that EGF induces binding of nuclear STAT3 to the TWIST promoter. Immunohistochemical analysis of 130 primary breast carcinomas indicates positive correlations between non-nuclear EGFR and TWIST and between phosphorylated STAT3 and TWIST. Together, we report here that EGF/EGFR signaling pathways induce cancer cell EMT via STAT3-mediated TWIST gene expression. [Cancer Res 2007;67(19):9066-76]

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Section: Methodsmentioning

confidence: 99%

Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-regulation of TWIST Gene Expression

et al. 2007

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“…Cp is also an antioxidant protein that blocks free oxygen radical-induced proteolysis and DNA damage through sequestration of free copper ions and superoxide anion radical scavengers, 28 and high levels of Cp expression have been demonstrated in various cancers such as thyroid carcinoma, melanoma and ovarian cancer. 29,30 In the present study, we attempted to explore how HIF-1a contributes to radio-resistance and chemo-resistance in OSCC cells. Abbreviations: AA, ascorbic acid; CDDP, cis-diamminedichloroplatinum; CoCl 2 , cobalt chloride; Cp, ceruloplasmin; CsA, cyclosporine A; 5-FU, 5-fluorouracil; HIF-1a, hypoxia-inducible factor-1a; HO-1, heme oxygenase-1; HRE, hypoxia-response element; MDR, multidrug resistance; Mn-SOD, manganese-superoxide dismutase; NAC, N-acetyl-L-cysteine; OSCC, oral squamous cell carcinoma; P-gp, P-glycoprotein; ROS, reactive oxygen species; siRNA, small interfering RNA; ZnPP, zinc protoporphyrin IX.…”

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confidence: 99%

The involvement of hypoxia‐inducible factor‐1α in the susceptibility to γ‐rays and chemotherapeutic drugs of oral squamous cell carcinoma cells

Sasabe

Zhou

et al. 2006

Intl Journal of Cancer

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The transcription factor hypoxia-inducible factor-1a (HIF-1a) is the key regulator that controls the hypoxic response of mammalian cells. The overexpression of HIF-1a has been demonstrated in many human tumors. However, the role of HIF-1a in the therapeutic efficacy of chemotherapy and radiotherapy in cancer cells is poorly understood. In this study, we investigated the influence of HIF-1a expression on the susceptibility of oral squamous cell carcinoma (OSCC) cells to chemotherapeutic drugs (cis-diamminedichloroplatinum and 5-fluorouracil) and c-rays. Treatment with chemotherapeutic drugs and c-rays enhanced the expression and nuclear translocation of HIF-1a, and the susceptibility of OSCC cells to the drugs and c-rays was negatively correlated with the expression level of HIF-1a protein. The overexpression of HIF-1a induced OSCC cells to become more resistant to the anticancer agents, and down-regulation of HIF-1a expression by small interfering RNA enhanced the susceptibility of OSCC cells to them. In the HIF-1a-knockdown OSCC cells, the expression of P-glycoprotein, heme oxygenase-1, manganese-superoxide dismutase and ceruloplasmin were downregulated and the intracellular levels of chemotherapeutic drugs and reactive oxygen species were sustained at higher levels after the treatment with the anticancer agents. These results suggest that enhanced HIF-1a expression is related to the resistance of tumor cells to chemo-and radio-therapy and that HIF-1a is an effective therapeutic target for cancer treatment. ' 2006 Wiley-Liss, Inc.Key words: hypoxia-inducible factor-1a; chemotherapeutic drugs; g-rays; P-glycoprotein; heme oxygenase-1 Solid tumors generally possess hypoxic areas in their central portion because of decreased vascular supply associated with the effects of treatment and the originally increased energy demand of cancer cells, and the hypoxic tissue is one of the serious matters for consideration in the control of malignant tumors. Most tumor cells possess the ability to undergo apoptosis in response to hypoxic conditions. However, tumor cells can adapt to hypoxic conditions by employing a variety of survival tools, which result in the promotion of cancer cell growth and metastasis. [1][2][3] This adaptation of cancer cells to hypoxia is mainly mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1). 4 HIF-1 is a heterodimeric transcription factor consisting of an oxygen-regulated a subunit (HIF1a) and a stable nuclear factor, HIF-1b/aryl hydrocarbon receptor nuclear translocator (ARNT). Under normoxic conditions, HIF-1a is rapidly degraded by the proteosome after being targeted for ubiquitination. HIF-1a translocates to the nucleus under hypoxic conditions and forms an active complex with HIF-1b; the complex binds to the hypoxia-response element (HRE) in the target genes, which results in the transactivation of these genes. 5 Proteins encoded by such genes contribute to the blood supply, energy production, growth/survival, invasion/metastasis and resistance.It has been frequently rep...

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“…Ceruloplasmin protein is expressed in pancreatic, nasopharyngeal and germline ovarian cancers (27). Ceruloplasmin promoter activation is specifically and efficiently enhanced in ovarian cancer (28).…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate biomarkers using the Experion™ automated electrophoresis system in serum samples from ovarian cancer patients

Kim

Park

et al. 2013

International Journal of Oncology

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Abstract. Ovarian cancer is the most common cause of diseaserelated death in women globally. Detection of ovarian cancer using new biomarkers is necessary for early diagnosis. To date, there have been no obvious biomarkers for ovarian cancer detection in the incipient stage. In this study, we discovered potential diagnostic serological biomarkers for ovarian cancer using the Experion™ automated electrophoresis system. Sera from 14 healthy women and 84 ovarian cancer patients at stages I-IV were applied to the Experion to compare the protein expression levels. To examine the protein expression pattern of Experion data, proteins in the samples were resolved using 10 and 15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by silver staining. The candidate biomarkers elevated in ovarian cancer were purified and determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. α-2-macroglobulin (173.7 kDa), ceruloplasmin (147 kDa), inter-α-trypsin inhibitor family heavy chain-related protein (126 kDa), C-1 inhibitor (115.2 kDa) and hemoglobin α/β (14.4 kDa were overexpressed in the ovarian cancer sera. This study documents a novel way to measure ovarian cancer or cancer-related proteins for biomarkers using the Experion assay system, which should be easily adaptable for high-throughput diagnosis to establish databases of ovarian cancer for clinical applications.

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Selective Activation of Ceruloplasmin Promoter in Ovarian Tumors

Cited by 36 publications

References 21 publications

Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-regulation of TWIST Gene Expression

Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-regulation of TWIST Gene Expression

The involvement of hypoxia‐inducible factor‐1α in the susceptibility to γ‐rays and chemotherapeutic drugs of oral squamous cell carcinoma cells

Identification of candidate biomarkers using the Experion™ automated electrophoresis system in serum samples from ovarian cancer patients

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