CHARACTERIZATION OF THE MAMMARY GLUCOCORTICOID RECEPTOR

乳腺糖皮质激素受体的特征

• 批准号: 3165973
• 负责人: FRANCIS S MARKLAND
• 金额: $ 12.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3165973
• 关键词: affinity chromatography; biopsy; cell nucleus; chemical fingerprinting; chemical group; cytoplasm; glucocorticoids; hormone regulation /control mechanism; hormone related neoplasm /cancer; mammary gland; molecular oncology; neoplasm /cancer diagnosis; radioimmunoassay

The objective of this study is to isolate and characterize the glucocorticoid receptor from a hormonally sensitive target organ, the lactating mammary gland. Our preliminary studies have shown lactating goat mammary tissue to be a good source of this protein. We have developed purification procedures that enable us to prepare a highly purified glucocorticoid receptor. The purified glucocorticoid receptor is being characterized physiochemically and the topography of the steroid binding site is being studied by the use of radioactive affinity-labeling steroid derivatives and site-specific protein modifying agents. Binding of the purified "activated" steroid-receptor complex to DNA-cellulose or nuclei isolated from target organs will be utilized to identify physiologically important cytoplasmic steroid binding macromolecules. The effect on nuclear binding of modification of specific amino acid residues in the receptor will be studied in order to identify nuclear attachment sites of the receptor protein. Additionally, the purified receptor will be used for the production of an antiserum that may be helpful in the development of sensitive immunoassays to detect steroid hormone receptors in biopsy specimens from women with breast cancer.

本研究的目的是分离和表征糖皮质激素 来自激素敏感靶器官（泌乳乳腺）的受体。 我们的初步研究表明，哺乳山羊的乳腺组织是一种良好的 这种蛋白质的来源。 我们开发了纯化程序，使 我们制备了高度纯化的糖皮质激素受体。 纯化后的 糖皮质激素受体的生理化学特征和 类固醇结合位点的拓扑结构正在通过使用进行研究 放射性亲和标记类固醇衍生物和位点特异性蛋白 改性剂。 纯化的“活化”类固醇受体复合物的结合 DNA-纤维素或从靶器官分离的细胞核将用于 识别生理上重要的细胞质类固醇结合大分子。 特定氨基酸残基修饰对核结合的影响 将研究该受体以确定其核附着位点 受体蛋白。 此外，纯化的受体将用于 生产可能有助于敏感疾病发展的抗血清 免疫分析检测女性活检标本中的类固醇激素受体 患有乳腺癌。

项目成果

Steroid derivatives for electrophilic affinity labelling of glucocorticoid binding sites: interaction with the glucocorticoid receptor and biological activity.

用于糖皮质激素结合位点亲电亲和标记的类固醇衍生物：与糖皮质激素受体的相互作用和生物活性。

• DOI: 10.1016/0022-4731(83)90054-7
• 发表时间: 1983
• 期刊: Journal of steroid biochemistry
• 作者: Weisz,A;Buzard,RL;Horn,D;Li,MP;Dunkerton,LV;MarklandJr,FS
• 通讯作者: MarklandJr,FS

Glucocorticoid receptor from lactating goat mammary tissue comparison of native and activated forms in a cell free system.

来自泌乳山羊乳腺组织的糖皮质激素受体在无细胞系统中天然形式和活化形式的比较。

• DOI: 10.1016/0022-4731(89)90509-8
• 发表时间: 1989
• 期刊: Journal of steroid biochemistry
• 作者: Hutchens,TW;Hawkins,EF;MarklandJr,FS
• 通讯作者: MarklandJr,FS

Physicochemical analysis of reversible molybdate effects on different molecular forms of glucocorticoid receptor.

钼酸盐对糖皮质激素受体不同分子形式的可逆作用的物理化学分析。

• DOI: 10.1016/0006-291x(81)91660-0
• 发表时间: 1981
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Hutchens,TW;Markland,FS;Hawkins,EF
• 通讯作者: Hawkins,EF

Clonal variants of a melanoma cell line sensitive to growth inhibition by dexamethasone.

对地塞米松生长抑制敏感的黑色素瘤细胞系的克隆变体。

• DOI: 10.1016/0014-4827(82)90187-2
• 发表时间: 1982
• 期刊: Experimental cell research
• 影响因子: 3.7
• 作者: Buzard,RL;Hutchens,TW;Hawkins,EF;Markland,FS;Horn,D
• 通讯作者: Horn,D

Competitive binding assay for glucocorticoids. Influence of experimental conditions on measurement of the affinity of competitive steroids for the receptor.

糖皮质激素的竞争性结合测定。

• DOI: 10.1016/0022-4731(82)90072-3
• 发表时间: 1982
• 期刊: Journal of steroid biochemistry
• 作者: Weisz,A;Hutchens,TW;MarklandJr,FS
• 通讯作者: MarklandJr,FS