scholarly journals Hepatocyte Growth Factor Inhibits Anoikis by Induction of Activator Protein 1-dependent Cyclooxygenase-2

2002 ◽  
Vol 277 (51) ◽  
pp. 50137-50142 ◽  
Author(s):  
Qinghua Zeng ◽  
Laurie K. McCauley ◽  
Cun-Yu Wang
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Cyclooxygenase 2 ◽  
Erk Signaling ◽  
Activator Protein 1 ◽  
Anoikis Resistance ◽  
Activator Protein ◽  
Cox 2 ◽  
Hepatocyte Growth

Anoikis, also called suspension-induced apoptosis, plays an important role in tumor development, progression, and metastasis. Recently we found that hepatocyte growth factor (HGF) inhibited anoikis of human head and neck squamous cell carcinoma (HNSCC) cells by activating the extracellular signal-regulated kinase (ERK)-signaling pathway. However, the anti-apoptotic effectors that were regulated by the ERK-signaling pathway were unknown. Here we report that HGF-mediated inhibition of anoikis was dependent on activator protein-1 activity through the activation of the ERK-signaling pathway. Using a combination of microarray analysis and Northern blot analysis, we found that an anti-apoptotic gene cyclooxygenase-2 (cox-2) was induced by HGF in an activator protein-1-dependent fashion. Inhibition of Cox-2 activity partially abolished HGF-mediated cell survival, and overexpression of Cox-2 in HNSCC cells provided resistance against anoikis. Moreover, HNSCC cells stably expressing Cox-2 had aggressive tumor growth in a nude mouse model compared with control cells. Taken together, our results demonstrate that Cox-2 plays an important role in HGF-mediated anoikis resistance. HGF may stimulate the progression and growth of HNSCCin vivoby induction of Cox-2.

Involvement of activator protein 1 complexes in the epithelium-specific activation of the laminin γ2-chain gene promoter by hepatocyte growth factor (scatter factor)

2000 ◽  
Vol 347 (2) ◽  
pp. 407-417 ◽  
Author(s):  
J⊘rgen OLSEN ◽  
Olivier LEFEBVRE ◽  
Christine FRITSCH ◽  
Jesper T. TROELSEN ◽  
Veronique ORIAN-ROUSSEAU ◽  
...  
Keyword(s):  
Growth Factor ◽  
Basement Membrane ◽  
Hepatocyte Growth Factor ◽  
Transforming Growth Factor ◽  
Regulatory Elements ◽  
Chain Gene ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
Cellular Expression ◽  
Hepatocyte Growth

Laminin-5 is a trimer of laminin α3, β3 and γ2 chains that is found in the intestinal basement membrane. Deposition of the laminin γ2 chain at the basement membrane is of great interest because it undergoes a developmental shift in its cellular expression. Here we study the regulatory elements that control basal and cytokine-activated transcriptional expression of the LAMC2 gene, which encodes the laminin γ2 chain. By using transient transfection experiments we demonstrated the presence of constitutive and cytokine-responsive cis-elements. Comparison of the transcriptional activity of the LAMC2 promoter in the epithelial HT29mtx cells with that in small-intestinal fibroblastic cells (C20 cells) led us to conclude that two regions with constitutive epithelium-specific activity are present between positions -1.2 and -0.12 kb. This was further validated by transfections of primary foetal intestinal endoderm and mesenchyme. A 2.5 kb portion of the LAMC2 5ʹ flanking region was equally responsive to PMA and hepatocyte growth factor (HGF), whereas it was less responsive to transforming growth factor β1. A minimal promoter limited to the initial 120 bp upstream of the transcriptional start site maintained inducibility by PMA and HGF. This short promoter fragment contains two activator protein 1 (AP-1) elements and the 5ʹ-most of these is a composite AP-1/Sp1 element. The 5ʹAP-1 element is crucial to the HGF-mediated activity of the promoter; analysis of interacting nuclear proteins demonstrated that AP-1 proteins containing JunD mediate the response to HGF.

scholarly journals Hepatocyte growth factor regulates cyclooxygenase-2 expression via β-catenin, Akt, and p42/p44 MAPK in human bronchial epithelial cells

2008 ◽  
Vol 294 (4) ◽  
pp. L778-L786 ◽  
Author(s):  
Young H. Lee ◽  
Yuichiro J. Suzuki ◽  
Autumn J. Griffin ◽  
Regina M. Day
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Gene Transcription ◽  
Bronchial Epithelial Cells ◽  
Cyclooxygenase 2 ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Cox 2 ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF) is upregulated in response to lung injury and has been implicated in tissue repair through its antiapoptotic and proliferative activities. Cyclooxygenase-2 (COX-2) is an inducible enzyme in the biosynthetic pathway of prostaglandins, and its activation has been shown to play a role in cell growth. Here, we report that HGF induces gene transcription of COX-2 in human bronchial epithelial cells (HBEpC). Treatment of HBEpC with HGF resulted in phosphorylation of the HGF receptor (c-Met), activation of Akt, and upregulation of COX-2 mRNA. Adenovirus-mediated gene transfer of a dominant negative (DN) Akt mutant revealed that HGF increased COX-2 mRNA in an Akt-dependent manner. COX-2 promoter analysis in luciferase reporter constructs showed that HGF regulation required the β-catenin-responsive T cell factor-4 binding element (TBE). The HGF activation of the COX-2 gene transcription was blocked by DN mutant of β-catenin or by inhibitors that blocked activation of Akt. Inhibition of p42/p44 MAPK pathway blocked HGF-mediated activation of β-catenin gene transcription but not Akt activation, suggesting that p42/p44 MAPK acts in a parallel mechanism for β-catenin activation. We also found that inhibition of COX-2 with NS-398 blocked HGF-induced growth in HBEpC. Together, the results show that the HGF increases COX-2 gene expression via an Akt-, MAPK-, and β-catenin-dependent pathway in HBEpC.

Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor by a RAS-RAF-MEK-ERK signaling pathway

Oncogene ◽  
2002 ◽  
Vol 21 (15) ◽  
pp. 2309-2319 ◽  
Author(s):  
Rejane Paumelle ◽  
David Tulashe ◽  
Zoulika Kherrouche ◽  
Serge Plaza ◽  
Catherine Leroy ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Scatter Factor ◽  
Hepatocyte Growth

scholarly journals Involvement of activator protein 1 complexes in the epithelium-specific activation of the laminin γ2-chain gene promoter by hepatocyte growth factor (scatter factor)

2000 ◽  
Vol 347 (2) ◽  
pp. 407 ◽  
Author(s):  
Jørgen OLSEN ◽  
Olivier LEFEBVRE ◽  
Christine FRITSCH ◽  
Jesper T. TROELSEN ◽  
Veronique ORIAN-ROUSSEAU ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Gene Promoter ◽  
Chain Gene ◽  
Activator Protein 1 ◽  
Scatter Factor ◽  
Activator Protein ◽  
Hepatocyte Growth

Coexpression of cyclooxygenase-2 (COX-2), hepatocyte growth factor (HGF) and gastrin in gastric cancer before and after eradication of Helicobacter pylori (Hp)

2001 ◽  
Vol 120 (5) ◽  
pp. A743-A744
Author(s):  
Peter C. Konturek ◽  
Stanislaw J. Konturek ◽  
Aleksandra Duda ◽  
Holger Meixner ◽  
Wladyslaw Bielanski ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cyclooxygenase 2 ◽  
Before And After ◽  
Cox 2 ◽  
Hepatocyte Growth

scholarly journals Erratum: Hepatocyte growth factor/scatter factor activates the ETS1 transcription factor by a RAS-RAF-MEK-ERK signaling pathway

Oncogene ◽  
2002 ◽  
Vol 21 (31) ◽  
pp. 4872-4872
Author(s):  
Rejane Paumelle ◽  
David Tulasne ◽  
Zoulika Kherrouche ◽  
Serge Plaza ◽  
Catherine Leroy ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Signaling Pathway ◽  
Erk Signaling ◽  
Scatter Factor ◽  
Hepatocyte Growth
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