| Inactivation of Rho GTPases by p190 RhoGAP reduces human pancreatic cancer cell invasion and metastasis. | |
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MedLine Citation:
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PMID: 16776779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A number of small GTPases are involved in cancer cell proliferation, migration and invasion, acting as molecular switches that cycle between GTP- and GDP-bound states. GTPase-activating proteins (GAPs) have been established as a major class of negative regulators of Rho GTPase signaling. To investigate the biological function of p190 RhoGAP toward RhoA in cancer cell invasion and metastasis, we generated a chimera made of the RhoGAP domain of p190 and the C-terminus of RhoA (p190-RhoA chimera), and transfected it into human pancreatic cancer cells, AsPC-1. Epidermal growth factor (EGF)-induced activation of RhoA, as well as RhoB and RhoC, to a lesser extent, was significantly inhibited in p190-RhoA chimera-transfected AsPC-1 cells compared with that of control cells (mock-infected), when assessed by pull-down assay for GTP-bound RhoA, RhoB, and RhoC, respectively. EGF-induced invasion of p190-RhoA chimera transfectants was significantly inhibited compared with that of mock-infected cells in a modified Boyden chamber assay. Furthermore, the mice injected intrasplenically with AsPC-1 cells that overexpressed the p190-RhoA chimera had a marked reduction in the number and size of metastatic nodules in the liver. These data suggest that the inhibitory action of p190 RhoGAP toward RhoA offers a novel approach to the treatment of invasion and metastasis of cancer cells. |
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Authors:
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Toshiyuki Kusama; Mutsuko Mukai; Hiroko Endo; Osamu Ishikawa; Masaharu Tatsuta; Hiroyuki Nakamura; Masahiro Inoue |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-06-14 |
Journal Detail:
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Title: Cancer science Volume: 97 ISSN: 1347-9032 ISO Abbreviation: Cancer Sci. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-08-18 Completed Date: 2006-10-18 Revised Date: 2011-09-27 |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: England |
Other Details:
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Languages: eng Pagination: 848-53 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Carrier Proteins / genetics, metabolism* Cell Line, Tumor Chimera DNA-Binding Proteins Enzyme Activation / drug effects, physiology Epidermal Growth Factor / pharmacology GTPase-Activating Proteins Guanine Nucleotide Exchange Factors Humans Mice Mitogen-Activated Protein Kinases / drug effects, metabolism Neoplasm Invasiveness / physiopathology* Neoplasm Transplantation Neoplasms, Experimental / pathology Pancreatic Neoplasms / enzymology, pathology* Repressor Proteins Transfection rho GTP-Binding Proteins / drug effects, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/ARHGAP35 protein, human; 0/ARHGAP5 protein, human; 0/Arhgap5 protein, mouse; 0/Carrier Proteins; 0/DNA-Binding Proteins; 0/GTPase-Activating Proteins; 0/Grlf1 protein, mouse; 0/Guanine Nucleotide Exchange Factors; 0/Repressor Proteins; 62229-50-9/Epidermal Growth Factor; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.6.5.2/rho GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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