15-lipoxygenase products in colorectal differentiation

15-脂氧合酶产品在结直肠分化中的作用

• 批准号: 6737888
• 负责人: AARON THOMAS JACOBS
• 金额: $ 4.3万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6737888
• 关键词: RNA interference; RNase protection assay; biological signal transduction; cell differentiation; cell growth regulation; cell line; colorectal neoplasms; enzyme activity; enzyme induction /repression; gel mobility shift assay; gene expression; isozymes; lipoxygenase; liquid chromatography mass spectrometry; microarray technology; neoplastic growth; oxidative stress; postdoctoral investigator; proteomics; transcription factor; ultraviolet spectrometry; western blottings

DESCRIPTION (provided by applicant): This postdoctoral training proposal evaluates the hypothesis that expression of 15-Lipoxygenase (15-Lox) mediates the differentiation of colorectal cancer cells, via the activation of peroxisome proliferator activated receptors (PPAR) gamma and alpha. Experiments will utilize the Caco-2 colon carcinoma cell line, in which 15-Lox is highly upregulated during spontaneous differentiation. Interestingly, a function for 15-Lox products in Caco-2 differentiation has yet to be established. Experiments will specifically address the contribution of the 15-Lox products, 15-HETE and 15-HETE-G in promoting the differentiation of Caco-2 cells into enterocytes. 15-HETE and 15-HETE-G have previously been demonstrated to activate PPARgamma and PPARalpha, respectively, transcription factors with established roles in growth-arrest and differentiation in a number of cell types. Therefore, experiments will further explore the contribution of 15-Lox activity, and 15-HETE and 15-HETE-G production in PPAR activation. The roles of individual PPARs in the differentiation process will also be examined. This research will be the first test for a biological role of 15-HETE-G. In addition, it will evaluate the role of 15-Lox and PPARs in promoting growth arrest in colorectal cancer, providing novel insight into the mechanisms of cancer biology.

描述（由申请人提供）：该博士后训练建议评估了以下假设：15-脂氧酶（15-LOX）的表达通过过氧化物酶体增殖物激活受体（PPAR）Gamma和alpha的激活介导了结直肠癌细胞的分化。 实验将利用CACO-2结肠癌细胞系，其中15-LOX在自发分化过程中高度上调。 有趣的是，尚未确定15-Lox产品的功能。 实验将特别解决15-Lox产物，15-HETE和15-HETE-G在促进Caco-2细胞分化为肠细胞中的贡献。 先前已证明15-HETE和15-HETE-G分别激活Ppargamma和Pparalpha，分别在许多细胞类型的生长降落和分化中既有作用''的转录因子。 因此，实验将进一步探讨PPAR激活中15-LOX活性以及15-HETE和15-HETE-G产生的贡献。 还将检查各个PPAR在分化过程中的作用。 这项研究将是15-HETE-G的生物学作用的首次测试。 此外，它将评估15-lox和PPAR在促进结直肠癌生长停滞中的作用，从而提供对癌症生物学机制的新见解。