CSF-1R EXPRESSION IN HUMAN BREAST CARCINOMA

描述：（改编自研究者摘要）基于 初步调查，总结在他们的身体 应用，他们已经证明，显着水平的CSF-1 R（ fms-原癌基因产物）由肿瘤性乳腺上皮表达 细胞在体内和体外;和激活这种受体对乳腺癌 癌细胞通过其同源配体，巨噬细胞集落刺激 因子CSF-1增加了 特异性蛋白酶和刺激基底膜的侵袭 类似物，如人羊膜和基质胶。 他们还 在体外证明，这种受体的表达水平大大降低， 糖皮质激素增强某些乳腺癌来源的培养细胞 线，但不是在其他地方。 基于这些观察，他们假设转录和 CSF-1 R的表达水平在（良性和肿瘤性） 乳腺上皮细胞的糖皮质激素和下调 拮抗剂，如RU-486在体内和体外。 他们还 假设第一个CSF-1 R的转录调节 糖皮质激素在乳腺癌细胞中进一步调节 通过一个或多个辅助转录因子来解释为什么 启动子在某些细胞系中对糖皮质激素有反应， 使CSF-1 R启动子响应于（或不应） 糖皮质激素--普遍存在的类固醇激素--可能会有帮助 解释了在体内观察到的CSF-1 R表达水平的差异， 乳腺癌标本。 他们建议通过继续调查以下问题来检验这些假设： 类固醇激素对CSF-1 R基因表达调控--特异性聚焦 关于第一个CSF-1 R的那些元素的更完整的表征 启动子（以及与它们结合的蛋白质）负责观察到的 刺激BT 20和SKBR 3中CSF-1 R基因转录，但不刺激MCF-7中CSF-1 R基因转录 乳腺癌细胞系，并确定表达水平是否 这些“辅助”因素与表达水平相关， 在人乳腺癌组织标本中观察到CSF-1 R。 他们还 建议确定糖皮质激素及其拮抗剂是否调节 CSF-1 R在乳腺癌组织中的表达维持在 在短期器官培养中体内和在裸鼠体内。

DESCRIPTION: (adapted from the investigator's abstract) Based on the preliminary investigations which are summarized in the body of their application, they have demonstrated that significant levels of CSF-1Rs (the fms-protooncogene product) are expressed by neoplastic mammary epithelial cells in vivo and in vitro; and that activation of this receptor on breast carcinoma cells by its cognate ligand, the macrophage-colony stimulating factor, CSF-1 increases the expression & cell surface localization of specific proteases and stimulates the invasion of basement membrane analogues such as human amnionic membrane and Matrigel. They have also demonstrated in vitro that levels of expression of this receptor are greatly augmented by glucocorticoids in some breast carcinoma-derived cultured cell lines, but not in others. Based on these observations, they have hypothesized that transcription and level of expression of CSF-1R is increased in (benign and neoplastic) mammary epithelial cells by glucocorticoids and down regulated by antagonists such as RU-486 in vivo and in vitro. They have also hypothesized that the regulation of transcription of the first CSF-1R promoter by glucocorticoids in breast carcinoma cells is further modulated by one or more accessory transcription factors which explain why this promoter is responsive to glucocorticoids in some cell lines and whose action in vivo to render the CSF-1R promoter responsive (or refractory) to glucocorticoids--ubiquitous and omnipresent steroid hormones--may help explain the variance in levels of CSF-1R expression observed in vivo in breast carcinoma specimens. They propose to test these hypotheses by continuing the investigations of steroid hormone regulation of CSF-1R gene expression--specifically focusing on the more complete characterization of those elements of the first CSF-1R promoter (and the proteins which bind to them) responsible for the observed stimulation of CSF-1R gene transcription in BT20 and SKBR3 but not MCF-7 breast carcinoma cell lines and determining whether the levels of expression of these "accessory" factors correlates with the level of expression of CSF-1R observed in human breast carcinoma tissue specimens. They also propose to determine whether glucocorticoids and their antagonists modulate the expression of CSF-1R in human breast carcinoma specimens maintained ex vivo in short-term organ culture and in vivo in nude mice.