CELL BIOLOGY AND TOPOLOGY OF THE REFRACTORY RAT MAMMARY GLAND

难治性大鼠乳腺的细胞生物学和拓扑结构

• 批准号: 6346036
• 负责人: BILL R BRINKLEY
• 金额: $ 15.41万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6346036
• 关键词: SDS polyacrylamide gel electrophoresis; cancer prevention; carcinogenesis inhibitor; cell cycle; cellular oncology; cellular pathology; chemical carcinogen; chemical carcinogenesis; confocal scanning microscopy; extracellular matrix proteins; flow cytometry; fluorescence microscopy; hormone regulation /control mechanism; human tissue; immunocytochemistry; in situ hybridization; laboratory rat; mammary epithelium; methylnitrosourea; molecular oncology; monoclonal antibody; neoplastic cell; nucleic acid probes; protein structure; radionuclide double label

This project will employ fluorescent imaging technology and biochemistry to investigate kinetic parameters and nuclear organization in epithelial cells of the rat mammary glands that are refractory to chemical carcinogens. Our aim will be accomplished by (1) defining and comparing the cell kinetics of the proliferative compartment in carcinogen sensitive mammary glands of virgin rats with mammary glands of animals made resistant to carcinogens by hormone treatment, 2) defining the topology and identifying the stages of the cell cycle of cells in the refractory glands and (3) characterizing nuclear domains and nuclear matrix protein patterns in mammary epithelial cells in the susceptible, resistant and malignant states. Our specific aims are to identify and characterize the proliferative compartment in the mammary gland of mature virgin and hormone treated rats and to determine the changes in the kinetics of proliferation after MNU treatment, and to identify structural changes in nuclear domains and characterize proteins of the nuclear matrix that may be specifically expressed in the mature virgin mammary glands and glands of animals made refractory to carcinogens after hormone treatment. The nuclear matrix proteins will also b analyzed in carcinogen-induced intraductal proliferations and in mammary adenocarcinoma. Antibodies will be made to nuclear matrix proteins which are unique to mammary epithelial cells of the resistant gland and to nuclear matrix proteins unique to adenocarcinoma cells. The antibodies will be used to characterize the topology of the cells of the resistant state and to follow the distribution and fate of resistant cells and adenocarcinoma cells.

该项目将利用荧光成像技术和生物化学来 研究上皮细胞的动力学参数和核组织 对化学致癌物耐药的大鼠乳腺。我们的 目标将通过(1)定义和比较细胞动力学 致癌物敏感的乳腺组织中的增殖室 处女大鼠的乳腺与动物的乳腺通过 激素治疗，2)定义拓扑学和识别阶段 难治性腺细胞的细胞周期和(3)特征 乳腺上皮细胞的核结构域和核基质蛋白模式 处于敏感、耐药和恶性状态的细胞。我们的特定 目的是确定和描述增殖性隔室在 成年处女大鼠乳腺及激素处理后的变化 MNU处理后细胞增殖动力学的变化 确定核结构域的结构变化并表征蛋白质 可能在成熟的处女体内特异表达的核基质 对致癌物具有抵抗力的动物乳腺和腺体 激素治疗。核基质蛋白也将在#年进行分析。 致癌物诱导的导管内和乳腺内增殖 腺癌。将产生针对核基质蛋白的抗体 是耐药腺体的乳腺上皮细胞所特有的 腺癌细胞所特有的核基质蛋白。抗体 将用于表征抗性细胞的拓扑结构 状态并跟踪耐药细胞的分布和命运 腺癌细胞。