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Biotech / Medical : Millennium Pharmaceuticals, Inc. (MLNM) -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (2718)	9/30/2006 1:22:17 PM
From: tuck	Respond to of 3044

[CXCR4 and EGFR] >>Cancer Res. 2005 Dec 15;65(24):11392-9. Widespread CXCR4 activation in astrocytomas revealed by phospho-CXCR4-specific antibodies. Woerner BM, Warrington NM, Kung AL, Perry A, Rubin JB. Department of Pediatrics, Division of Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA. The chemokine receptor CXCR4 is expressed in many cancers where it may regulate tumor cell growth and migration. The role of CXCR4 in cancer will depend on it being in an activated, signaling state. To better define the significance of CXCR4 expression in cancer, we developed an antibody that can distinguish CXCR4 phosphorylated on serine 339, a residue previously identified as a site for ligand-induced phosphorylation. With this antibody, we investigated the mechanisms of CXCR4 phosphorylation and evaluated the phosphorylation status of CXCR4 in human astrocytomas. In vitro, phosphorylation of serine 339 occurred in response to CXCL12 or epidermal growth factor (EGF) treatment and was increased by protein kinase C activation. In all grades of astrocytomas, CXCR4 was expressed in tumor cells and some endothelial cells, whereas CXCL12 was present in endothelial cells and infiltrating microglia. We found that CXCR4 phosphorylated on serine 339 was present in tumor cells and vascular endothelial cells in all grades of astrocytoma. These data indicate that CXCR4 is expressed and activated in astrocytomas and that phosphorylation of CXCR4 can occur through ligand activation or transactivation via the EGF receptor. These studies extend the potential roles of CXCR4 in cancer to include functions associated with benign (grade 1) tumors. The ability to distinguish phosphorylated CXCR4 will be invaluable for the continued analysis of the role of CXCR4 in cancer and the development of CXCR4 antagonist therapy for patients suffering with primary tumors of the brain and other sites.<< I never understood GENZ' interest in AnorMED in the first place. It would seem a better fit with players more focused on cancer in general, and since the above hints at synergy with EGFR inhibitors, and in particular with folks like OSI (though maybe Goddard is a little gunshy on expensive munches by now), and various BPs, such as BMY. Cheers, Tuck