Involvement of the mitogen-activated protein kinase kinase 2 in the induction of cell dissociation in pancreatic cancer

Tan, Xiaodong; Egami, Hiroshi; Kamohara, Hidenobu; Ishikawa, Satoshi; Kurizaki, Takashi; Yoshida, Naoya; Tamori, Yasuhiko; Takai, Eiji; Hirota, Masahiko; Ogawa, Michio

doi:10.3892/ijo.24.1.65

Cited by 16 publications

(27 citation statements)

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“…We identified mitogen-activated protein kinase kinase 2 (MEK2) as a factor that was correlated with the invasion and metastasis potential of these cell lines (4). Further investigation confirmed that MEK2 was involved in invasion/metastasis of both hamster and human pancreatic cancer cells (5).…”

Section: Introductionmentioning

confidence: 52%

“…In the present study, we knocked down MEK1 and MEK2 expression to examine their functions in the progression of pancreatic cancer. Although certain smallmolecule inhibitors of MEK1/2 (e.g., U0126) have been tested as potential candidates for cancer therapy (5,19), most of the inhibitors target MEK1 and MEK2 simultaneously (20). Therefore, these inhibitors lack specificity.…”

Section: Discussionmentioning

confidence: 99%

“…An aliquot of 1 μg of total RNA from each sample was reverse-transcribed to cDNA using the SuperScript II kit (Life Technologies, Inc.) as previously described (5). The specific PCR primer sequences for MEK1, MEK2 and ß-actin were: MEK1 forward: 5'-ATTATTGTTC CCCTAAGTGGATTG-3', reverse: 5'-TTACAACAGCATT GGTACTTGGAT-3'; MEK2 forward: 5'-GCAGTCGGACA TCTGGAGCA-3', reverse: 5'-CACCGTTG GGCAGCTTA GGA-3'; ß-actin forward: 5'-GTGGGGCGCCCCAGGCA CCA-3', reverse: 5'-CTCCTTAAGTCACGCACGATTCC-3'.…”

Section: Analysis Of Mek1 and Mek2 Mrna Expressions By Rt-pcrmentioning

confidence: 99%

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MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells

Zhou

Tan²,

Kamohara³

et al. 2010

Oncol Rep

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Abstract. 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 shRNAmediated 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 G 0 /G 1 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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Section: Introductionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Mek1 and Mek2 Mrna Expressions By Rt-pcrmentioning

confidence: 99%

See 1 more Smart Citation

MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells

Zhou

Tan²,

Kamohara³

et al. 2010

Oncol Rep

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“…To evaluate the expression of Tjp-2 protein and the relationship between the expression of Tjp-2 and cell dissociation in pancreatic cancer cells, either the conditioned medium of PC-1.0 cells (DF-CM) or the specific MEK inhibitor U0126 (cell Signaling Technology, Ma, uSa) were applied to Pc-1 and Pc-1.0 cells, respectively (5,13). For activation studies, dF-cM was added to the Pc-1 cells at a total concentration of 40%, then cells were incubated for 36 h. For inhibition studies, Pc-1.0 cells were incubated with 10 µM u0126 for 36 h. additionally, where noted, Pc-1 cells were incubated with 10 µM u0126 for 36 h following the incubation with dF-cM.…”

Section: Methodsmentioning

confidence: 99%

“…in further investigations, dF was found to activate the mitogen-activated protein kinase kinase 2 (MeK2)/extracellular signal-regulated kinase 2 (erK2) signal pathway, which was identified as a pivotal signalling pathway related to cell dissociation in Pc-1.0 and Pc-1 cells (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

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

Zhou

Tan²,

Wang³

et al. 2009

Mol Med Rep

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Abstract. 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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A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis

et al. 2010

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Purpose Pancreatic cancer is the fourth leading cause of cancer death in the United States, and new drugs to treat the disease are needed. Pancreatic cancer cells are highly metastatic and exhibit resistance to apoptosis. Small molecules that can restore sensitivity to apoptosis or reduce metastasis would have therapeutic potential against this disease. Manzamine A is an alkaloid isolated from marine sponges that was suspected to have inhibitory activity against the mitogen activated kinase kinase (MEK). Because of this, the effects of Manzamine A were studied in pancreatic cancer cells. Methods AsPC-1 cells were treated for 48 h in the presence of various concentrations of Manzamine A and their phenotype, cytotoxicity, cell invasion and susceptibility to apoptosis were observed. Results Manzamine A decreased single cell formation, abrogated cell migration and restored the susceptibility of the cells to TRAIL-induced apoptosis in AsPC-1 cells. Its mechanism of action remains unknown, as manzamine A does not inhibit MEK. Conclusions Manzamine A appears to have a formerly unrecognized activity in blocking tumor cell invasion as well as in restoring cancer cell susceptibility to apoptosis in vitro and therefore has the potential to be used as an adjuvant to existing cancer therapies.

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Involvement of the mitogen-activated protein kinase kinase 2 in the induction of cell dissociation in pancreatic cancer

Cited by 16 publications

References 0 publications

MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells

MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells

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

A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis

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