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Dissection of CXCR4 and CXCR7 mediated signaling in breast cancer

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Dissection of CXCR4 and CXCR7 mediated signaling in breast cancer

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Samenvatting

The involvement of G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) in several
diseases has been widely studied and reported. Chemokines and chemokine receptors are well known to be
involved in leukocyte trafficking and inflammation. Furthermore, some family members have shown to be
overexpressed in cancer. CXCR4 and its ligand CXCL12 have been widely studied and are known that they
play an important role in cancer. Recently, it was found that CXCL12 is able to bind another novel
chemokine receptor CXCR7. This receptor is also overexpressed in many different cancers and in addition to
CXCL12, CXCR7 binds with lower affinity to the chemokine CXCL11. Specific alleles of CXCL12 are
associated with and increases the risk of breast cancer, and CXCL12 has been shown to transactivate Her2/neu (ErbB2) through its receptor CXCR4, an established oncogene in breast cancer. ErbB family receptors are RTKs from which is also known to be overexpressed in cancers. ErbB2 is overexpressed in 25% - 30% of breast cancer and is associated with poor prognosis and shorter survival. The crosstalk between CXCR7 and ErbB2 in breast cancer is not yet clarified.
The BT-474 breast cancer cell line which expresses CXCR4, CXCR7 and ErbB2, was used in this project to
get a clear picture of the cross-talk occurring between these receptors. Using both 3H thymidine
incorporation and cell titer blue assays, the proliferation of BT474 cells was found to be initiated not only by
CXCR4 but working together with HER2 and CXCR7. There is an indication that CXCR4 and CXCR7 are
involved in the phosphorylation of ErbB2 and ErbB3 kinases. CXCR4, CXCR7 ErbB2 might be involved in
the proliferation and downstream signaling via p44/42 MAPK and AKT.

Toon meer
OrganisatieAvans Hogeschool
OpleidingBiologie en Medisch Laboratoriumonderzoek-Breda
AfdelingATGM Academie voor de technologie van Gezondheid en Milieu
PartnerVU Amsterdam, Medicinal Chemistry
Datum2013-05-24
TypeBachelor
TaalEngels

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