Hypoxia enhances MUC1 expression in a lung adenocarcinoma cell line

Mikami, Yuji; Hisatsune, Akinori; Tashiro, Tomomi; Isohama, Yoichiro; Katsuki, Hiroshi

doi:10.1016/j.bbrc.2009.01.002

Cited by 32 publications

(22 citation statements)

References 28 publications

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“…In a recent study of clear renal cell carcinoma, MUC1 was found to be a transcriptional target of hypoxia inducible factor 1 α (HIF1-α), which is upregulated in metastatic cancer, and promotes migration and invasion. 54 Hypoxia-enhanced MUC1 transcription was also observed in a human lung adenocarcinoma cell line, 55 demonstrating that control of MUC1 levels by hypoxia is not tissue-specific. Furthermore, MUC1 is transcriptionally upregulated by STATs in response to interferon gamma (IFNγ) and interleukin-6 (IL-6) signaling.…”

Section: Muc1 Expression Correlates With Metastasismentioning

confidence: 94%

MUC1 and metastatic cancer

Horm

Schroeder

2013

Cell Adhesion & Migration

163

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Section: Muc1 Expression Correlates With Metastasismentioning

confidence: 94%

MUC1 and metastatic cancer

Horm

Schroeder

2013

Cell Adhesion & Migration

163

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“…After a 6-day treatment of high glucose with or without HIF-1a inhibition, cells grown in 24-well plates were transfected with PGL2TkHRE by using the transfection reagent Lipofectamine 2000 (Invitrogen, Carlsbad, CA). As a positive control, cobalt chloride at 100 lM was added to cells 24 h after transfection [37]. Forty-eight hours after the transfection, luciferase activity was measured with the Luciferase Assay System (Promega, Madison, WT) on a micro-plate Luminometer (Berthold, Oak Ridge, TN).…”

Section: Plasmid Transfection and Luciferase Activity Assaymentioning

confidence: 99%

HIF-1 is involved in high glucose-induced paracellular permeability of brain endothelial cells

Yan

Zhang

Shi

2011

Cell. Mol. Life Sci.

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Experimental evidence from human patients and animal models of diabetes has demonstrated that hyperglycemia increases blood-brain barrier (BBB) permeability, which is associated with increased risk of neurological dysfunction. However, the mechanism underlying high glucose-induced BBB disruption is not understood. Here we investigated the role of hypoxia-inducible factor-1 (HIF-1) in high glucose-induced endothelial permeability in vitro using mouse brain microvascular endothelial cells (b.End3). Our results demonstrated that high glucose (30 mM) upregulated the protein level of HIF-1α, the regulatable subunit of HIF-1, and increased the transcriptional activity of HIF-1 in the endothelial cells. At the same time, high glucose increased the paracellular permeability associated with diminished expression and disrupted continuity of tight junction proteins occludin and zona occludens protein-1 (ZO-1) of the endothelial cells. Upregulating HIF-1 activity by cobalt chloride increased the paracellular permeability of the endothelial cells exposed to normal glucose (5.5 mM). In contrast, downregulating HIF-1 activity by HIF-1α inhibitors and HIF-1α specific siRNA ameliorated the increased paracellular permeability and the alterations of distribution pattern of occludin and ZO-1 induced by high glucose. In addition, high glucose increased expression of vascular endothelial growth factor (VEGF), a downstream gene of HIF-1. Inhibiting VEGF improved the expression pattern of occludin and ZO-1, and attenuated the endothelial leakage. Furthermore, key results were confirmed in human brain microvascular endothelial cells. These results strongly indicate that HIF-1 plays an important role in high glucose-induced BBB dysfunction. The results will help us understand the molecular mechanisms involved in hyperglycemia-induced BBB dysfunction and neurological outcomes.

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“…MUC1 overexpression correlates with high metastatic potential and poor survival; therefore, MUC1 antigens have been used as clinical markers to monitor disease progression in cancer patients (Kohno et al, 1992;Duffy et al, 2000). In addition, previous studies have shown that MUC1 has a pivotal role in tumor development, growth, invasion (Sachdeva and Mo, 2010), oncogenic cellular signal transduction (Raina et al, 2004;Wei et al, 2006), responses to hypoxia (Mikami et al, 2009) and resistance to anti-cancer reagents (Fessler et al, 2009). However, the significance of high expression of MUC1 in tumor cells remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Mucin 1 enhances the tumor angiogenic response by activation of the AKT signaling pathway

Woo

Choi

et al. 2011

Oncogene

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Although the hyper-glycosylated transmembrane protein Mucin 1 (MUC1) is aberrantly overexpressed in human breast carcinoma, the biological significance of MUC1 overexpression is unclear. This study showed that MUC1 expression promoted the synthesis and secretion of vascular endothelial growth factor (VEGF) through the AKT signaling pathway. Increase VEGF production through MUC1 expression had a number of effect. First, MUC1 transfection increased expression of VEGF in breast cancer cells. Second, MUC1-mediated VEGF induction was attenuated by a chemical inhibitor of AKT or MUC1 knock-down by MUC1 siRNA. Third, MUC1 expression led to the activation of insulin-like growth factor-1 receptor, which correlated with VEGF expression. In addition, when MDA-MB-231 human breast cancer cells were directly injected into NOD/SCID mice, MUC1 expression accelerated xenograft tumor growth in vivo. Finally, MUC1 expression enhanced tumor growth and angiogenesis in a PyMT-MMTV/ hMUC1 transgenic mouse model. Concurrent with these results, analysis of a human tissue microarray identified a high correlation between MUC1 and VEGF expression in human breast carcinoma. The current report is the first to demonstrate that MUC1 expression promotes angiogenesis in human breast cancer in vivo and in vitro.

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Hypoxia enhances MUC1 expression in a lung adenocarcinoma cell line

Cited by 32 publications

References 28 publications

MUC1 and metastatic cancer

MUC1 and metastatic cancer

HIF-1 is involved in high glucose-induced paracellular permeability of brain endothelial cells

Mucin 1 enhances the tumor angiogenic response by activation of the AKT signaling pathway

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