Survival Signaling in Breast Cancer

乳腺癌中的生存信号

• 批准号: 6732116
• 负责人: Suzanne Daniela Conzen
• 金额: $ 12.97万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-11 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732116
• 关键词: adrenocorticotropic hormone; apoptosis; athymic mouse; breast neoplasms; corticosteroid receptors; corticosterone; dexamethasone; enzyme activity; epidermal growth factor; gene induction /repression; glucocorticoids; hormone regulation /control mechanism; human tissue; immunocytochemistry; insulin; mifepristone; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; neoplastic growth; nonhuman therapy evaluation; protein kinase; receptor expression

Suzanne Conzen, M.D., recieved a balaurate degree, magna cum laude from Brown University, Her first exposure to bench science was in Dr. Charles Janeway, Jr's labortory at Yale Medical School . Following her second year of medical school she obtained an M.Sc. At the University of Tropical Medicine and Science before graduating from Yale in 1987. Following an internal medince residency at Cornell Medical Center she did her hematology and oncology fellowships at Dartmounth. Dr. Conzen wa awarded a Howard Hughes Physician Fellowship to study mechanism OS Sv40 mediated transformation in the Dartmouth Biochemistry under the mentorship of Dr. Chuck Cole. Dr. Conzen then moved to the University of Chicago's Ben May Institute to do a postdoctoral fellowship in the labortory of Dr. Nauseam Hay where she studied tumor-associated mutant c-Myc-medication apoptosis andd cell cycle progression. In 1998 Dr. Conzen was appointed Assistant Prefacer at the University of Chicago and established a research program studying mammary epithelial cell survival under the mentioship of Dr. Geoffrey Greene, director of the Breast Cancer Program at the Inversed of Chicago Cancer Cent. Dr. Conzen's work has shown that the glucocorticoid receptor (GR) has potent signaling effects in mammary epithelium and can transcriptionaly activate cell cycle-related kinases hypothesized to be important for cell survival and division. Because Dr. Conzen has little previous experience in steriod receptor biology or the analysis of intracelluar kinnase-mediated signaling pathways, the proposed research career development plan requests support to provide a comprehensive training period to work closely with Drs. Greene andd Marsha Rosner to determine the mechanism of GR- medicated survival signaling in breast cancer. Dr. Conzen proposes to characterize the gluocorticoid repersiveness and GR alpha and beta expression in breast tumor cell lines and to conurrently investigate the signaling pathways of GR-induced or repressed cellular kinase including SGK( serum and glucocorticoid induible kinases). Under the mentorship of Dr. Greene and with the assistance of Dr. Shutsung Liao and Dr. Mark Ratain, Dr. Conzen also proposes to eastablish anddan in vivo system to evaluate the GR in human breast cancer using an ER/PR negative human mammary carsinoma xenograft nude mouse model. The proposed career development plan will formulize Dr. Conzen's mentoring program with a defined research plan and ensure the protected research time needed for training in the methods and anyalytical skills required to develop an independent research program in survival signaling in malignant and normal breast epithelium.

Suzanne Conzen 医学博士以优异的成绩从布朗大学获得了学士学位，她第一次接触实验室科学是在耶鲁大学医学院 Charles Janeway Jr 博士的实验室。在医学院学习第二年后，她获得了硕士学位。 1987 年从耶鲁大学毕业之前，曾就读于热带医学与科学大学。在康奈尔医学中心完成内科住院医师实习后，她在达特蒙斯大学获得了血液学和肿瘤学奖学金。 Conzen 博士获得了霍华德休斯医师奖学金，在 Chuck Cole 博士的指导下研究达特茅斯生物化学中 OS Sv40 介导的转化机制。随后，Conzen 博士前往芝加哥大学 Ben May 研究所，在 Nauseam Hay 博士的实验室进行博士后研究，研究肿瘤相关突变 c-Myc 药物凋亡和细胞周期进展。 1998 年，Conzen 博士被任命为芝加哥大学助理序言人，并在芝加哥癌症中心乳腺癌项目主任 Geoffrey Greene 博士的指导下建立了一个研究乳腺上皮细胞存活的研究项目。 Conzen 博士的工作表明，糖皮质激素受体 (GR) 在乳腺上皮中具有有效的信号传导作用，并且可以转录激活细胞周期相关激酶，这些激酶被认为对细胞存活和分裂很重要。由于 Conzen 博士之前在类固醇受体生物学或细胞内激酶介导的信号通路分析方面几乎没有经验，因此拟议的研究职业发展计划需要支持，以提供全面的培训期，以便与 Drs 密切合作。 Greene 和 Marsha Rosner 确定了乳腺癌中 GR 药物生存信号传导的机制。 Conzen 博士建议表征乳腺肿瘤细胞系中糖皮质激素的重复性以及 GR α 和 β 表达，并同时研究 GR 诱导或抑制的细胞激酶（包括 SGK（血清和糖皮质激素诱导激酶））的信号传导途径。在 Greene 博士的指导下，在 Shutsung Liao 博士和 Mark Ratain 博士的协助下，Conzen 博士还建议建立 anddan 体内系统，利用 ER/PR 阴性的人类乳腺癌来评估人类乳腺癌的 GR异种移植裸鼠模型。拟议的职业发展计划将制定 Conzen 博士的指导计划和明确的研究计划，并确保在恶性和正常乳腺上皮生存信号传导独立研究计划所需的方法和分析技能培训方面提供受保护的研究时间。