Identification of TGF-B regulated angiogenesis genes

TGF-B调节的血管生成基因的鉴定

• 批准号: 6694872
• 负责人: Allan R Albig
• 金额: $ 4.16万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6694872
• 关键词: angiogenesis; cell line; cell migration; cell proliferation; gene expression; genetic regulation; microarray technology; polymerase chain reaction; postdoctoral investigator; tissue /cell culture; transforming growth factors; western blottings

DESCRIPTION (provided by applicant): Angiogenesis is a highly complex and ordered process whereby new blood vessels are formed from preexisting blood vessels. Angiogenesis is critically important for the development and maintenance of normal tissues, and for the progression of many human diseases including cancer. Because angiogenesis is required to support advanced progression of many diseases, it is thought that halting angiogenesis holds potential for minimizing disease progression. TGF-B is believed to be a powerful regulator of normal and abnormal angiogenesis, but the molecular mechanisms by which TGF-B regulates angiogenesis are largely unknown. The experiments in this proposal are designed to test the hypothesis that TGF-B signaling regulates the expression of genes required for proper blood vessel formation, and that these genes in turn regulate key steps in new blood vessel formation. In testing this hypothesis, we aim to (1) discover novel genes involved in the process of angiogenesis; (2) discover novel TGF-B regulated genes involved in the process of angiogenesis; and (3) characterize identified genes based on their effects on essential steps for proper angiogenesis. In meeting these aims we will discover and characterize novel genes which are important for controlling angiogenesis and may therefore one day, be used as molecular targets for small molecules designed to slow or halt angiogenesis thus improving clinical outcomes for cancer patients.

描述（由申请人提供）：血管生成是一个高度复杂且有序的过程，通过先前存在的血管形成新的血管。血管生成对于正常组织的发展和维持至关重要，对于包括癌症在内的许多人类疾病的发展。由于需要血管生成以支持许多疾病的先进进展，因此人们认为停止血管生成有可能最大程度地减少疾病进展。 TGF-B被认为是正常和异常血管生成的强大调节剂，但是TGF-B调节血管生成的分子机制在很大程度上尚不清楚。该提案中的实验旨在检验以下假设：TGF-B信号传导调节适当血管形成所需的基因表达，而这些基因又调节了新血管形成的关键步骤。在检验这一假设时，我们旨在（1）发现与血管生成过程有关的新基因； （2）发现与血管生成过程有关的新型TGF-B调节基因； （3）根据其对适当血管生成的基本步骤的影响来表征鉴定的基因。在满足这些目标时，我们将发现并表征新的基因，这些基因对于控制血管生成很重要，因此可能有一天被用作小分子的分子靶标，用于减慢或停止血管生成，从而改善癌症患者的临床结果。