Document Detail
Stroma-Derived SDF-1 Confers Chemoresistance to CXCR4-Expressing Breast Cancer Cells
Abstract/OtherAbstract :
The chemokine receptor CXCR4 is functionally expressed on the cell surface of various cancer cells, and plays a role in cell proliferation and migration of these cells. Specifically, in breast cancer cells the CXCR4/CXCL12 axis has been implicated in cell migration in vitro and in metastasis in vivo, but the underlying signaling mechanisms are incompletely understood. The xenograft-derived MDA-MB-231 breast cancer cell line (231mfp), which was shown previously to grow more aggressively than the parent cells, showed increased CXCR4 expression at the mRNA, total protein and cell surface expression level. This correlated with an enhanced response to CXCL12, specifically in augmented and prolonged Akt activation in a Gi, Src family kinase and PI-3 kinase dependent fashion. 231mfp cells migrated towards CXCL12 in contrast to the parent cell line and this chemotaxis was blocked by inhibition of Gi, Src family kinases, PI-3 kinase and interestingly, Akt itself, as could be shown with two pharmacological inhibitors, a dominant negative Akt construct and with Akt shRNA. Collectively, we have demonstrated that prolonged Akt activation is an important signaling pathway for breast cancer cells expressing CXCR4 and is necessary for CXCL12-dependent cell migration.
Authors :
Schraufstatter, Ingrid
Related Documents :
3173353 - Hrpap20: a novel tumor progression regulator in human breast cancer
10814153 - Laminin-5 β3a expression in lncap human prostate carcinoma cells increases cell migrat...
7487613 - Amphidinium carterae
Contributors :
LA JOLLA INST FOR MOLECULAR MEDICINE SAN DIEGO CA
Publication Detail :
Publisher :  -     Type :  Text     Format :  text/html    
Date Detail :
2007-10-01
Subject :
ANATOMY AND PHYSIOLOGY, MEDICINE AND MEDICAL RESEARCH, *BREAST CANCER, *CELLS(BIOLOGY), SURFACE PROPERTIES, SIGNALS, MIGRATION, INHIBITORS, IN VIVO ANALYSIS, PHARMACOLOGY, CANCER, CHEMOTAXIS, PHOSPHORUS TRANSFERASES, METASTASIS, IN VITRO ANALYSIS, ACTIVATION, PROTEINS
Coverage :
-
Relation :
-
Source :
DTIC
Copyright Information :
Approved for public release; distribution is unlimited.
Other Details :
Languages :  en    
Export Citation :
APA/MLA Format     Download EndNote     Download BibTex

Previous Document:  Targeting Signal Transducers and Activators of Transcription-3 (Stat3) As a Novel Strategy In Sensit...
Next Document:  Genetic Dissection of the Role of Heparan Sulfate in Mammary Tumor Progression