Role of Na,K ATPase in the development of carcinoma

Na,K ATP酶在癌症发生中的作用

• 批准号: 6536073
• 负责人: CROMWELL E ESPINEDA
• 金额: $ 2.48万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-12 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6536073
• 关键词: MDCK cell; athymic mouse; cadherins; cell motility; cellular polarity; enzyme activity; epithelium; gene induction /repression; kidney cell; kidney neoplasms; neoplasm /cancer genetics; neoplasm /cancer invasiveness; oncoproteins; sodium potassium exchanging ATPase

Each year, people are diagnosed with over one hundred diseases that are classified as different types of cancer, the second leading cause of death in the United States. In 1999 alone, over 1.2 million people were affected by cancer. Malignant tumors are most dangerous when they metastasize or spread throughout the body. This occurs when cancerous cells from a tumor enter the bloodstream and invade into tissues and organs. Recently, our laboratory found that inhibition of the Na,K pump results in increased intracellular sodium in kidney epithelial cells, which induces a signal transduction pathway leading to metastasis. Differential display screening revealed that one of the key players in this pathway is the MDM2 oncoprotein, which is responsible for degradation of p53, a tumor suppressor protein. The main goal of this research is to understand the significance of the induction of AMID upon inhibition of the sodium pump and to characterize the consequence of MDM2 overexpression in polarized kidney epithelial cells.

每年，人们被诊断患有一百多种不同类型的癌症，这是美国第二大死因。仅 1999 年，就有超过 120 万人受到癌症的影响。当恶性肿瘤转移或扩散到全身时，它们是最危险的。当肿瘤中的癌细胞进入血液并侵入组织和器官时，就会发生这种情况。最近，我们实验室发现抑制Na,K泵会导致肾上皮细胞内钠离子增加，从而诱导信号转导途径导致转移。差异显示筛选显示，该途径的关键参与者之一是 MDM2 癌蛋白，它负责肿瘤抑制蛋白 p53 的降解。本研究的主要目标是了解抑制钠泵时诱导 AMID 的重要性，并表征极化肾上皮细胞中 MDM2 过度表达的后果。