NDLI: Recepteur d'origine nantais tyrosine kinase is a direct target of hypoxia-inducible factor-1alpha-mediated invasion of breast carcinoma cells.

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Recepteur d'origine nantais tyrosine kinase is a direct target of hypoxia-inducible factor-1alpha-mediated invasion of breast carcinoma cells.

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Recepteur d'origine nantais tyrosine kinase is a direct target of hypoxia-inducible factor-1alpha-mediated invasion of breast carcinoma cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ammanamanchi, Sudhakar Thangasamy, Amalraj Rogge, Jessica
Description	Author Affiliation: Thangasamy A ( Department of Medicine, Division of Hematology and Medical Oncology, and Cancer Therapy & Research Center, University of Texas Health Science Center, San Antonio, Texas 78229.)
Abstract	Hypoxia-inducible factor-1alpha (HIF-1alpha) overexpression was shown to be associated with invasion and metastasis of tumors and tumor cell lines. The identification of molecular targets that contribute to HIF-1alpha-mediated invasion is under intensive investigation. We have analyzed the role of recepteur d'origine nantais (RON), a tyrosine kinase receptor for macrophage-stimulating protein (MSP) that plays a role in breast cancer cell invasion as one of the molecular targets of HIF-1alpha. Analysis of a panel of breast cancer cell lines indicated a correlation between HIF-1alpha and RON expression. Treatment of HIF-1alpha- and RON-positive breast cancer cells with HIF-1alpha inhibitor, echinomycin, led to the inhibition of HIF-1alpha activity and RON expression. We have identified HIF-1alpha binding site on the RON promoter. Chromatin immunoprecipitation analysis and site-directed mutagenesis of the RON promoter confirmed the binding of HIF-1alpha to RON promoter. HIF-1alpha inhibitor-, echinomycin-, or short hairpin RNA-mediated selective knockdown of HIF-1alpha or HIF-1alpha target RON tyrosine kinase abrogated RON gene expression, and the RON ligand macrophage-stimulating protein mediated invasion of breast cancer cells. Consequently, the data presented herein demonstrated RON as a novel molecular target of HIF-1alpha and suggest a potential therapeutic role for HIF-1alpha or RON tyrosine kinase inhibitors in the blockade of RON tyrosine kinase-mediated invasion of carcinoma cells.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	21
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-05-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Breast Neoplasms Enzymology Pathology Hypoxia-Inducible Factor 1, Alpha Subunit Metabolism Receptor Protein-Tyrosine Kinases Genetics Cell Extracts Cell Line, Tumor Echinomycin Pharmacology Extracellular Signal-Regulated MAP Kinases Antagonists & Inhibitors Gene Expression Regulation, Neoplastic Drug Effects Gene Knockdown Techniques Hepatocyte Growth Factor Neoplasm Invasiveness Phosphatidylinositol 3-Kinases Promoter Regions, Genetic Proto-Oncogene Proteins RNA, Small Interfering Research Support, N.I.H., Extramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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