CSF1 AND CSF1R AND BREAST AND OVARIAN CARCINOMA

描述：(改编自调查人员的摘要)基于他们的 他们观察到，他们在上一次更新资金期间所作的观察 几个卵巢癌来源的细胞系和肿瘤标本 表达缺少外显子2的CSF-1R转录本，该转录本包含翻译 全长蛋白质起始点和两个不同的磷酸酪氨酸 CSF-1R的残基似乎与蛋白酶相关 生产、侵袭性或转磷酸化其他 感受器。他们还获得了证据表明，到目前为止，一小部分60 KDA 未知蛋白与周围序列的CSF-1R结合 包括TYR-723，后者被磷酸化。 在他们目前的应用中，他们建议进一步研究这些 观察并确定1)剪接所编码的蛋白质 变异的卵巢癌CSF-1R转录本和定义它们的 生化和生理功能与野生型有关 CSF-1R蛋白，特别是与结构性自磷酸化有关的 TYR与无外源或自分泌的细胞转化 CSF-1来源；2)这些CSF-1R转录本和 它们在体内编码的N末端截短的蛋白质在良性和 肿瘤卵巢上皮细胞；3)无论是诱因还是基因改变 在Y723远端阻断信号转导的哪一个模拟Y--&F突变 并显著减少(如果不是取消)CSF-1R对乳房的刺激 上皮细胞锚定非依赖性生长和致瘤性；4) 以产生针对我们Y809周围的多肽的单抗 该位点酪氨酸磷酸化的CSF-1R与其他位点的鉴别 配体激活的酪氨酸激酶，如EGF-R、HER-2/neu和c-Met。

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.