scholarly journals Signaling pathway involved in cyclooxygenase-2 up-regulation by hepatocyte growth factor in endometrial cancer cells

2011 ◽  
Author(s):  
Yoshihiko Yamada
2003 ◽  
Vol 13 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Y.-H. Park ◽  
H.-S. Ryu ◽  
D.-S. Choi ◽  
K.-H. Chang ◽  
D.-W. Park ◽  
...  

Matrix metalloproteinase (MMP)-2 and -9 are secreted and translocated from endometrial stromal cells to HEC-1 A cells in a steroid-dependent manner. We investigated the paracrine effect of hepatocyte growth factor (HGF) on MMPs and metalloproteinase tissue inhibitor (TIMP) expression in stromal and endometrial cancer cells, and correlated with cancer cell invasiveness in three-dimensional (3D) coculture. The 3D coculture of endometrial stromal and cancer cell lines (HEC-1 A, HEC-IB, or KLE) were maintained in the presence or absence of HGF. The expression of MMP-2 and -9, MT1-MMP, TIMP-1 and -2 were examined by RT-PCR and zymography. Under the same conditions, invasion of the cancer cells was quantified by Boyden's chamber assay. HGF strongly induced MMP-9 mRNA expression in stromal cells, but had little effect on MMP-2 mRNA. MT1-MMP mRNA was detected only in KLE and stromal cells, which was also increased by HGF. TIMP-1 and -2 mRNAs was ubiquitous with no dependence on HGF. Zymographic analysis of MMPs showed that activation of MMP-2 and -9 was enhanced by HGF. A significant increase in invasion of all three cancer cells with HGF was observed. The effect of HGF on the invasiveness of 3D cocultured endometrial cancer cells and stromal cells appears to be due to induction of MMP-9 mRNA expression in stromal cells and /or increased activation of MMP-2 and MMP-9 by proteolytic digestion.


2002 ◽  
Vol 277 (51) ◽  
pp. 50137-50142 ◽  
Author(s):  
Qinghua Zeng ◽  
Laurie K. McCauley ◽  
Cun-Yu Wang

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.


Author(s):  
Kyung Hee Lee ◽  
Eun Young Choi ◽  
Min Kyoung Kim ◽  
Myung Soo Hyun ◽  
Jong Ryul Eun ◽  
...  

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