CSF1 AND CSF1R AND BREAST AND OVARIAN CARCINOMA

描述：（改编自研究者的摘要）基于他们的

DESCRIPTION: (adapted from the investigator's abstract) Based on their observations made during their last period of renewal funding, they observe that several ovarian carcinoma derived cell lines and tumor specimens express a CSF-1R transcript lacking exon 2 which contains the translation start site for the full-length protein and that two distinct phosphotyrosine residues of the CSF-1R appear to be correlated either with protease production, invasiveness or the ability to transphosphorylate other receptors. They also have obtained evidence that a small 60 kda heretofore unknown protein binds to the CSF-1R at the sequence surrounding and including TYR-723 when the latter is phosphorylated. In their current application, they propose to further investigate these observations and determine 1) whether the protein encoded by the splice variant ovarian carcinoma CSF-1R transcripts and define how their biochemical and physiological functions relate to those of the wild-type CSF-1R protein, specifically with regard to constitutive autophosphorylation on TYR and cell transformation in the absence of exogenous or autocrine sources of CSF-1; 2) whether the expression of these CSF-1R transcripts and the N-terminally truncated proteins they encode in vivo in benign and neoplastic ovarian epithelial cells; 3) whether agents or genetic changes which block signal transduction distal to Y723 mimic Y-->F mutations at that site and markedly diminish (if not abolish) CSF-1R stimulation of mammary epithelial cell anchorage-independent growth and tumorigenicity; 4) whether to produce monoclonal antibodies to our peptide surrounding Y809 able to discriminate CSF-1R phosphorylated on tyrosine at this site from other ligand-activated tyrosine kinases such as EGF-R, HER-2/neu, and c-met.