CSF-1R EXPRESSION IN HUMAN BREAST CARCINOMA

描述：(改编自调查人员的摘要)基于 初步调查总结在其正文中 应用，他们已经证明了显著水平的CSF-1RS( FMS-原癌基因产物)由肿瘤性乳腺上皮细胞表达 体内和体外细胞；以及乳房上该受体的激活 肿瘤细胞通过其同源配体-巨噬细胞集落刺激 因子，CSF-1增加细胞表面的表达和定位 特异性蛋白水解酶与刺激基底膜侵袭 类似物，如人羊膜和Matrigel。他们还拥有 体外实验证明，该受体的表达水平极高 糖皮质激素对某些乳腺癌培养细胞的增强作用 线条，但不是在其他地方。 基于这些观察，他们假设转录和 良性和肿瘤性疾病中CSF-1R的表达水平升高 糖皮质激素对乳腺上皮细胞的作用及其下调作用 如RU-486等拮抗剂在体内和体外。他们还拥有 假设第一个CSF-1R的转录调控 糖皮质激素对乳腺癌细胞启动子的进一步调控 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，其 体内作用使CSF-1R启动子对 糖皮质激素--一种普遍存在的类固醇激素--可能会有所帮助 解释在体内观察到的CSF-1R表达水平的变化 乳腺癌标本。 他们建议通过继续调查这些假设来检验这些假设 类固醇激素对CSF-1R基因表达的调节--特异性聚焦 关于第一个CSF-1R的那些元件的更完整的表征 启动子(以及与其结合的蛋白质)对观察到的 BT20和SKBR3细胞对CSF-1R基因转录的刺激作用，但对MCF-7细胞无刺激作用 并测定乳腺癌细胞株的表达水平 这些“辅助性”因素中的一种与 人乳腺癌组织标本中观察到的CSF-1R。他们也 建议确定糖皮质激素及其拮抗剂是否调节 人乳腺癌标本中CSF-1R的表达 短期器官培养体内和裸鼠体内。

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.