E1AF/PEA3 reduces the invasiveness of SiHa cervical cancer cells by activating serine proteinase inhibitor squamous cell carcinoma antigen

Iwasaki, Masanori; Nishikawa, Akira; Akutagawa, Noriyuki; Fujimoto, Takashi; Teramoto, Mizue; Sakaguchi, Yuko; Katô, Hiroshi; Ito, Miyuki; Yoshida, Kôichi; Kudo, Ryuichi

doi:10.1016/j.yexcr.2004.06.020

Cited by 17 publications

(14 citation statements)

References 29 publications

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“…pLNTK-E1AF-infected SiHa cells were cultured in DMEM supplemented with 10% FBS and 0.03% glutamine at 37jC in an atmosphere of 5% CO 2 and used for positive control for Western blot analysis of E1AF protein (30).…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analyses of E1AF were done as previously described (30). Briefly, purified total protein (30 Ag) from isolated subconfluent cells was separated by SDS-PAGE, transferred to nitrocellulose membranes, and reacted with an anti-E1AF monoclonal antibody (a gift from Dr. Chono, Takara Bio, Otsu, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…The primary antibody was detected using an antirabbit antibody conjugated with horseradish peroxidase and visualized by the Amersham enhanced chemiluminescence (ECL) system (Amersham, Arlington Heights, IL). pLNTK-E1AF-infected SiHa cells were used for positive control of E1AF protein expression (30). The same lysates were used in Western blotting of actin as an internal control.…”

Section: Methodsmentioning

confidence: 99%

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E1AF/PEA3 Activates the Rho/Rho-Associated Kinase Pathway to Increase the Malignancy Potential of Non–Small-Cell Lung Cancer Cells

Hakuma

Kinoshita²,

Shimizu³

et al. 2005

Cancer Research

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E1AF/PEA3, an Ets family transcription factor, is frequently overexpressed in non-small-cell lung cancers (NSCLCs). Overexpression of E1AF increases motility and invasion of VMRC-LCD and NCI-H226 NSCLC cells, which lack endogenous E1AF expression, and the effect is synergistically increased by hepatocyte growth factor (HGF). The small GTPase Rho/Rhoassociated kinase (ROCK) pathway is also involved in motility and invasion. To determine the role of the Rho/ROCK pathway in malignant phenotypes induced by E1AF, we analyzed VMRC-LCD cells transfected with an E1AF expression vector (LCD-E1AF cells) or with empty vector (LCD-vector cells). LCD-E1AF cells had more GTP-bound (active) Rho than LCD-vector cells and Rho activation was synergistically increased by HGF. The Rho activation by E1AF and HGF was also shown in NCI-H226 cells. Phosphorylation of myosin light chain (MLC), a downstream effector of ROCK signaling, was higher in LCD-E1AF cells than in LCD-vector cells, especially under HGF treatment. A specific ROCK inhibitor, Y27632, strongly suppressed MLC phosphorylation, cell motility, and invasion. In nude mice implanted s.c. and intrapulmonarily, LCD-E1AF cells made more local tumors than LCD-vector cells (six of six versus one of seven mice and four of seven versus one of seven mice, respectively). Three of the four mice with lung tumors from LCD-E1AF cells had lymph node metastases whereas the mouse with LCD-vector tumors did not. LCD-E1AF tumors showed higher MLC phosphorylation than LCD-vector tumors. These results suggest that E1AF activates the Rho/ROCK pathway in an HGF-enhanced manner and its activation is important in E1AF-induced motility and invasion as well as tumorigenesis and metastasis in NSCLC cells. (Cancer Res 2005; 65(23): 10776-82)

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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E1AF/PEA3 Activates the Rho/Rho-Associated Kinase Pathway to Increase the Malignancy Potential of Non–Small-Cell Lung Cancer Cells

Hakuma

Kinoshita²,

Shimizu³

et al. 2005

Cancer Research

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“…After the detachment from the primary tumor, cancer cells migrate, attach to vessels, and move to other organs through blood and lymph fluid flow. In fact, suppression of SCCA2 expression promoted cell invasion and cell migration with the decreased expression of E-cadherin [29,30].Blockage of E-cadherin action suppressed SCCA production in squamous cell carcinoma cell lines [31]. Our immunohistochemical study on cervical squamous cell carcinoma revealed that SCCA2 expression was significantly related with E-cadherin expression and that mixed pattern with loss and positive stained of SCCA2 and E-cadherin in primary lesions was strongly associated with high incidence of lymph node metastasis [32].…”

Section: Role Of Scca In Squamous Cell Carcinoma Of Uterine Cervixmentioning

confidence: 99%

Involvement of Squamous Cell Carcinoma Antigen in Invasion and Metastasis of Squamous Cell Carcinoma of Uterine Cervix

Murakami¹,

Yoshidomi²,

Sugino³

2012

Squamous Cell Carcinoma

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“…Mutations of transcription factors and changes in signalling pathways affect transcription factor activity and significantly contribute to a wide range of human diseases [23][24][25]. Thus, GSTFs are very promising targets for pharmaceutical intervention (see the next chapter).…”

Section: The Influence Of Snps On Gene Expression -Their Effects On Tmentioning

confidence: 99%

The emerging importance of DNA mapping and other comprehensive screening techniques, as tools to identify new drug targets and as a means of (cancer) therapy personalisation

Kroczak

Baran

Pryjma

et al. 2006

Expert Opinion on Therapeutic Targets

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Every human being is genetically unique and this individuality is not only marked by morphologic and physical characteristics but also by an individual's response to a particular drug. Single nucleotide polymorphisms (SNPs) are largely responsible for one's individuality. A drug may be ineffective in one patient, whereas the exact same drug may cure another patient. Recent advances in DNA mapping and other screening technologies have provided researchers and drug developers with crucial information needed to create drugs that are specific for a given individual. In the future, physicians will be able to prescribe individualised drugs adjusted to, for example, activities of specific enzymatic pathways that would either be targeted by these drugs, or would be responsible for drug conversion or inactivation. Furthermore, the mapping of the human genome allows broader development and application of drugs that act on the level of gene transcription rather than as simple biochemical inhibitors or activators of certain enzymes. Such new approaches will maximise desired therapeutic results and may completely eliminate severe side effects. To illustrate the potential of genetic translational research, the authors discuss available analytical methodologies such as; gene arrays, flow cytometry-based screening for SNPs, proteomics, metabolomics, real-time PCR, and other methods capable of detecting both SNPs, as well as more profound changes in cell metabolism. Finally, the authors provide several examples that focus mostly on targeting protein-DNA interactions, but also other processes

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E1AF/PEA3 reduces the invasiveness of SiHa cervical cancer cells by activating serine proteinase inhibitor squamous cell carcinoma antigen

Cited by 17 publications

References 29 publications

E1AF/PEA3 Activates the Rho/Rho-Associated Kinase Pathway to Increase the Malignancy Potential of Non–Small-Cell Lung Cancer Cells

E1AF/PEA3 Activates the Rho/Rho-Associated Kinase Pathway to Increase the Malignancy Potential of Non–Small-Cell Lung Cancer Cells

Involvement of Squamous Cell Carcinoma Antigen in Invasion and Metastasis of Squamous Cell Carcinoma of Uterine Cervix

The emerging importance of DNA mapping and other comprehensive screening techniques, as tools to identify new drug targets and as a means of (cancer) therapy personalisation

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