PMID- 22960271
OWN - NLM
STAT- MEDLINE
DCOM- 20130403
LR  - 20130201
IS  - 1096-0945 (Electronic)
IS  - 0014-4800 (Linking)
VI  - 94
IP  - 1
DP  - 2013 Feb
TI  - Protease-activated receptor 2 signaling upregulates angiogenic growth factors in 
      renal cell carcinoma.
PG  - 91-7
LID - S0014-4800(12)00119-0 [pii]
LID - 10.1016/j.yexmp.2012.08.005 [doi]
AB  - Renal cell carcinoma (RCC) is a highly vascular tumor associated with expression 
      of various angiogenic growth factors. The precise process of how these growth 
      factors are regulated in RCC is not fully understood. Recent evidence suggests 
      that protease activated receptors (PARs), a new family of G-protein coupled 
      receptors, play a crucial role in vascular development and tumor progression 
      through a variety of mechanisms. However, the nature of PAR expression in human 
      RCC tissues and its function in regulating angiogenesis in RCC are largely 
      unknown. In this study, we investigated the expression and function of PAR-2 in 
      RCC. RT-PCR and immunohistochemistry assays show that PAR-2 expression is 
      significantly increased in human RCC tissue compared with the adjacent 
      non-neoplastic kidney tissue. In RCC derived cells, PAR-2 is functional as 
      evidenced by robust signaling through MAP kinases including ERK1/2 and JNK. 
      Furthermore, activation of PAR-2 significantly upregulates several angiogenic 
      cytokines, including interleukin-6 (IL-6), IL-8, monocytes chemotactic protein-1 
      (MCP-1) and growth-related oncogene (GRO). To our knowledge, this is the first 
      report that characterized PAR-2 expression in RCC tissue and further demonstrated 
      that PAR-2 has a critical role in regulating angiogenesis in RCC.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Zhang, Xiaotun
AU  - Zhang X
AD  - Department of Urology, University of Washington, Seattle, Washington 98195, 
      United States. xiaotun@u.washington.edu
FAU - Wang, Wenbin
AU  - Wang W
FAU - Mize, Gregory J
AU  - Mize GJ
FAU - Takayama, Thomas K
AU  - Takayama TK
FAU - True, Lawrence D
AU  - True LD
FAU - Vessella, Robert L
AU  - Vessella RL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120831
PL  - Netherlands
TA  - Exp Mol Pathol
JT  - Experimental and molecular pathology
JID - 0370711
RN  - 0 (Angiogenic Proteins)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CXCL1 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptor, PAR-2)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Angiogenic Proteins/*biosynthesis
MH  - Carcinoma, Renal Cell/blood supply/*metabolism
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/biosynthesis
MH  - Chemokine CXCL1/biosynthesis
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Interleukin-6/biosynthesis
MH  - Interleukin-8/biosynthesis
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Kidney Neoplasms/blood supply/*metabolism
MH  - MAP Kinase Signaling System
MH  - *Neovascularization, Pathologic
MH  - Receptor, PAR-2/*metabolism
MH  - Up-Regulation
EDAT- 2012/09/11 06:00
MHDA- 2013/04/04 06:00
CRDT- 2012/09/11 06:00
PHST- 2012/05/08 00:00 [received]
PHST- 2012/06/25 00:00 [revised]
PHST- 2012/08/23 00:00 [accepted]
PHST- 2012/09/11 06:00 [entrez]
PHST- 2012/09/11 06:00 [pubmed]
PHST- 2013/04/04 06:00 [medline]
AID - S0014-4800(12)00119-0 [pii]
AID - 10.1016/j.yexmp.2012.08.005 [doi]
PST - ppublish
SO  - Exp Mol Pathol. 2013 Feb;94(1):91-7. doi: 10.1016/j.yexmp.2012.08.005. Epub 2012 
      Aug 31.