Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our previous investigation, mitogen-activated protein kinase kinase 2 (MEK2) was detected as a factor which was correlated to the potential of invasion-metastasis. In this study, the immunocytochemical, immunohistochemical and mRNA expressions of MEK2 were examined in pancreatic cancer cell lines and tissue samples, respectively. Constitutive expressions of MEK2 and phosphorylated MEK (p-MEK) were observed in PC-1.0 and ASPC-1 cells, which exhibited a growth pattern of single cells, whereas the relevant expressions were quite faint in PC-1 cells and CAPAN-2 cells, which exhibited a growth pattern of island-like clonies. Simultaneous inductions of MEK2 expressions and cell dissociation were observed after the treatment with a conditioned medium (CM) of PC-1.0 cells. The expression of MEK2 and p-MEK were reduced and the cell aggregation was found in PC-1.0 and ASPC-1 cells after U0126 (a MEK inhibitor) treatment. In vivo, both the MEK2 and p-MEK overexpressed in human pancreatic cancer tissues and p-MEK was found to be more strongly expressed in the invasive front than that in the center of tumor (P<0.05). MEK2 is closely related to pancreatic cancer cell dissociation. MEK2 activation is probably involved in the first step of the cascade in the invasion-metastasis of pancreatic cancer.
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PMID:Involvement of the mitogen-activated protein kinase kinase 2 in the induction of cell dissociation in pancreatic cancer. 1465 42

Mitogen-activated protein kinase kinase 2 (MEK2), the upstream kinase of extracellular signal-regulated kinase 1/2 (ERK1/2) was previously isolated as cancer cell dissociation related factor. In this study, to further clarify the regulatory mechanism of cancer cell dissociation, two hamster (PC-1.0 and PC-1) and human (Capan-2 and AsPC-1) pancreatic cancer cell lines were analyzed immunocytochemically with anti-ERK1, anti-ERK2 and anti-phosphorylated ERK1/2 (p-ERK1/2) antibodies. U0126 (a MEK1/2 inhibitor) significantly suppressed ERK2 and p-ERK1/2 expressions in PC-1.0 and AsPC-1 cells (P<0.05). Cancer cell dissociation factor (DF) markedly induced ERK2 and p-ERK1/2 expressions in PC-1 and Capan-2 cells (P<0.05), and the induced ERK2 and p-ERK1/2 expressions were inhibited by subsequent U0126-treatment (P<0.05). Simultaneously, light microscopic images showed that DF clearly induced cell dissociation in PC-1 and Capan-2 cells, while U0126-treatment induced cell aggregation in these pancreatic cancer cells. ERK2 activation is closely involved in cell dissociation of pancreatic cancer cells.
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PMID:Relationship between the expression of extracellular signal-regulated kinase 1/2 and the dissociation of pancreatic cancer cells: Involvement of ERK1/2 in the dissociation status of cancer cells. 1501 Aug 17

Mitogen-activated protein kinase kinase 2 (MEK2) was detected as an invasion-metastasis related factor between highly invasive (PC-1.0) and weakly invasive (PC-1) pancreatic cancer cell lines in our previous study. On the other hand, tight junction (TJ) was found to be correlated with carcino-genesis and tumor development. In this study, the expressions and correlation of TJ transmembrane protein occludin and MEK/extracellular signal-regulated kinase (ERK) signaling pathway were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines were analyzed immunocytochemically with anti-occludin, phosphorylated MEK1/2 (p-MEK1/2), phosphorylated ERK1/2 (p-ERK1/2) antibodies. MEK1/2 inhibitor U0126 significantly induced the expression of occludin at the cell-cell junction and substantially suppressed the p-MEK1/2 and p-ERK1/2 expressions in PC-1.0 and AsPC-1 cells. In contrast, dissociation factor (DF) treatment obviously disrupted the occludin expressions at the sites of cell-cell junction and markedly induced the p-MEK1/2 and p-ERK1/2 expressions in PC-1 and CAPAN-2 cells. In addition, occludin expressions at cell-cell junction were restored and p-MEK1/2 and p-ERK1/2 expressions were suppressed by subsequent U0126-treatment in DF treated PC-1 and CAPAN-2 cells. Correspondingly, light microscopic images showed that DF induced the dissociation of cell island-like colonies in PC-1 and CAPAN-2 cells, and U0126-treatment induced cell aggregation in these pancreatic cancer cells. Occludin is involved in the cell dissociation in pancreatic cancer cells. Moreover, MEK/ERK signaling pathway probably regulates the cell dissociation status of pancreatic cancer through influencing the intracellular localization and expression of occludin.
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PMID:Analysis of invasion-metastasis mechanism in pancreatic cancer: involvement of tight junction transmembrane protein occludin and MEK/ERK signal transduction pathway in cancer cell dissociation. 1506 37

In our previous investigations, mitogen-activated protein kinase kinase 2 (MEK2)/extracellular signal-regulated kinase 2 (ERK2) signaling pathway was found to be correlated with the cell dissociation induced by dissociation factor (DF) in pancreatic cancer cells. In this study, the expressions of epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and its downstream kinases MEK1/2 and ERK1/2, were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and two human (AsPC-1 and Capan-2) pancreatic cancer cell lines were used. Immunocytochemical study was performed using anti-EGFR, p-EGFR, phosphorylated MEK1/2 (p-MEK1/2), and phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF-treatment markedly induced the expressions of EGFR, p-EGFR, p-MEK1/2, p-ERK1/2, as well as the dissociation of cell colonies in PC-1 and Capan-2 cells. In contrast, AG1478 (an EGFR inhibitor) treatment significantly induced the cell aggregation in PC-1.0 and AsPC-1 cells which usually grew as single cells, but strongly suppressed the expressions of EGFR, p-EGFR, p-MEK1/2, and p-ERK1/2. These observations demonstrate that activation of EGFR is closely involved in cell dissociation in pancreatic cancer through activating MEK/ERK signaling pathway.
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PMID:Relationship between activation of epidermal growth factor receptor and cell dissociation in pancreatic cancer. 1549 19

Mitogen-activated protein kinase kinase 2 (MEK2) was isolated previously as a potential factor related to cancer cell dissociation in highly (PC-1.0) and weakly (PC-1) invasive pancreatic cancer cells. On the other hand, changes of structure and function of tight junction (TJ) are reported to be correlated with carcinogenesis and tumor development. In this study, immunocytochemistry and Western blot analysis were performed in pancreatic cancer cells using anti-claudin-1, MEK2 and phosphorylated MEK1/2 (p-MEK1/2) antibodies to reveal the correlation between TJ and cancer cell dissociation, as well as the involvement of MEK2 in regulation of TJ in cell dissociation of pancreatic cancer. After incubation with conditioned medium of PC-1.0 cells, plasma membrane distribution of claudin-1 was obviously disrupted, and expressions of MEK2 and p-MEK1/2, as well as dissociation of cell colonies, were significantly induced in PC-1 and CAPAN-2 cells. However, U0126 (a MEK1/2 inhibitor) treatment apparently induced the plasma membrane distribution of claudin-1 and aggregation of single cells in PC-1.0 and AsPC-1 cells, synchronously seriously suppressed MEK2 and p-MEK1/2 expression. Arrangement of expression and distribution of claudin-1 is closely related to cell dissociation status in pancreatic cancer cells through MEK2 activation.
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PMID:Arrangement of expression and distribution of tight junction protein claudin-1 in cell dissociation of pancreatic cancer cells. 1554 92

Epidermal growth factor receptor (EGFR) mediated mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway was isolated as invasion-metastasis related factor in pancreatic cancer in our previous studies. Matrix metalloproteinase-7 (MMP-7) and tight junction (TJ) proteins are indicated to be involved in cancer invasion-metastasis. To clarify the underlying mechanism of involvement of MMP-7 in cancer invasion, western blotting, invasion assay and immunohistochemistry were performed in dissociated (PC-1.0 and AsPC-1) and non-dissociated (PC-1 and Capan-2) pancreatic cancer cells, as well as pancreatic cancer tissues. Intracellular MMP-7 protein presented as pre-proenzyme and its expression was decreased by AG1478 (EGFR inhibitor) or U0126 (MEK inhibitor) treatment in pancreatic cancer cells. Activated MMP-7 protein was only detected in the medium of PC-1.0 and AsPC-1 cells, but not detected in the medium of PC-1 and Capan-2 cells. Moreover, MMP-7 treatment significant induced the dissociation of cell colonies in PC-1 and Capan-2 cells. Synchronously, TJ structure was apparently disrupted and translocation of TJ proteins to cytoplasm or extracellular medium was induced in PC-1 and Capan-2 cells. Furthermore, MMP-7 treatment markedly increased the in vitro invasion of PC-1 and Capan-2 cells. In addition, MMP-7 expression at the invasive front was obviously stronger than that at the center of pancreatic cancer tissues. Activation of MMP-7 protein is closely involved in disruption of TJ structure and consequent induction of cell dissociation as well as invasion in pancreatic cancer. EGFR mediated MEK/ERK signaling pathway is implied to be involved in regulation of MMP-7 expression in pancreatic cancer cells.
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PMID:Involvement of matrix metalloproteinase-7 in invasion-metastasis through induction of cell dissociation in pancreatic cancer. 1580 19

In our previous study, dissociation factor (DF) and mitogen-activated protein kinase kinase 2 (MEK2) were isolated as factors relating to cancer cell dissociation in pancreatic cancer cells. On the other hand, tight junction protein zonula occludens 1 (ZO-1) has been indicated to be involved in carcinogenesis. In this study, the expression of ZO-1 and a downstream kinase of MEK2, extracellular signal-regulated kinase 2 (ERK2), was analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and two human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines were used. Immunocytochemical study was performed using anti-ZO-1, ERK2, and phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF treatment obviously disrupted ZO-1 expression at the sites of cell-cell contact and markedly induced ERK2 and p-ERK1/2 expression, as well as the dissociation of cell clones in PC-1 and CAPAN-2 cells. In contrast, U0126 (a MEK1/2 inhibitor) treatment significantly induced the peripheral distribution of ZO-1 as well as cell aggregation in PC-1.0 and AsPC-1 cells, which usually grew as single cells, but seriously suppressed ERK2 and p-ERK1/2 expression. We conclude that redistribution of ZO-1 is closely correlated with cell dissociation status in pancreatic cancer cells through activation of ERK2.
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PMID:Zonula occludens-1 (ZO-1) redistribution is involved in the regulation of cell dissociation in pancreatic cancer cells. 1611 Aug 28

The mitogen-activated protein kinase kinase 1/2 (MEK1/2) signalling pathway plays a central role in tumour progression. Small molecules that inhibit MEK1/2 are therefore considered attractive candidates for anti-cancer drugs. However, the exact contributions of MEK1 and MEK2 to the development of pancreatic cancer remain to be established. To differentiate the functions of MEK1 and MEK2 in a cultured pancreatic cancer cell line, we utilised shRNA-mediated knockdown of their two mRNAs individually. We studied the effects of MEK1 and MEK2 knockdown on cell morphology, proliferation, mitotic arrest, and in vitro invasion capability in PC-1.0 cells. The results showed that inhibition of MEK1 expression was an effective and specific approach to inhibit cell proliferation and induce G0/G1 arrest. On the other hand, MEK2 knockdown specially altered cell morphology and inhibited the invasive ability of pancreatic cancer cells. Therefore, MEK1 and MEK2 mediate different biological responses in cultured pancreatic cancer cells. These proteins could become distinct targets for the inhibition of specific cellular functions in the treatment of pancreatic cancer.
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PMID:MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells. 2051 69

High frequency of invasion and metastasis is one of the key characteristics of pancreatic cancer. In our recent study, tight junction protein-2 (Tjp-2) was identified as a differentially expressed gene related to invasion-metastasis in highly (PC-1.0) and weakly (PC-1) invasive and metastatic pancreatic cancer cells by cDNA microarray analysis. Changes in the structure and function of tight junctions are correlated with carcinogenesis and tumour development. In this study, RT-PCR, Western blotting and immunocytochemistry were used to study the correlation between the expression and localisation of Tjp-2 and cell dissociation in pancreatic cancer. Tjp-2 mRNA and protein were differentially expressed in PC-1.0 and PC-1 cells. Furthermore, the addition of dissociation factor (DF) or U0126 (a MEK inhibitor) significantly induced changes in the mRNA expression and protein intracellular localisation of Tjp-2, and in the simultaneous cell dissociation of PC-1.0 and PC-1 cells. However, protein expression of Tjp-2 was not affected by DF or U0126 treatment. The current results indicate that Tjp-2 is involved in the regulation of cell dissociation in pancreatic cancer cells through changes in gene expression and intracellular localisation. Tjp-2 may serve as a new target for molecular therapies that prevent the invasion and metastasis of pancreatic cancer.
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PMID:Analysis of invasion-metastasis in pancreatic cancer: Correlation between the expression and arrangement of tight junction protein-2 and cell dissociation in pancreatic cancer cells. 2147 14

Dissociation of pancreatic cancer cells from primary sites is the critical first step in tumour invasion and metastasis. Changes in the structure and function of tight junctions are reported to be correlated with carcinogenesis and tumour development. Using cDNA microarray analysis, we recently identified claudin-23 as a differentially expressed gene related to invasion-metastasis in highly (PC-1.0) and weakly (PC-1) invasive and metastatic pancreatic cancer cells. In this study, RT-PCR, Western blotting and immunocytochemistry were used to demonstrate the involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation. Claudin-23 mRNA and protein were differentially expressed in PC-1.0 and PC-1 cells. Claudin-23 expression was induced in a PC-1.0 subclone expressing mitogen-activated protein kinase kinase (MEK)-1 short-hairpin RNA (shRNA) and claudin-23 was redistributed in a PC-1.0 subclone expressing MEK2 shRNA. Furthermore, these MEK2 shRNA-expressing PC-1.0 cells aggregated and formed island-like cell colonies. By contrast, the addition of dissociation factor-conditioned medium significantly reduced claudin-23 mRNA and protein expression in PC-1 cells. The present results indicate that claudin-23 is involved in the regulation of pancreatic cancer cell dissociation through changes in gene expression and intracellular localisation. In addition, claudin-23 expression is possibly correlated with the activation of the MEK signalling pathway during pancreatic cancer cell dissociation. Claudin-23 may thus serve as a new target for molecular therapies to prevent pancreatic cancer invasion and metastasis.
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PMID:Involvement of the expression and redistribution of claudin-23 in pancreatic cancer cell dissociation. 2147 24


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