15-lipoxygenase products in colorectal differentiation

描述（由申请人提供）：该博士后培训计划评估了15-脂氧合酶（15-Lox）的表达通过激活过氧化物酶体增殖物激活受体（PPAR）γ和α介导结直肠癌细胞分化的假设。 实验将利用Caco-2结肠癌细胞系，其中15-Lox在自发分化期间高度上调。 有趣的是，15-Lox产物在Caco-2分化中的功能尚未建立。 实验将具体说明15-Lox产物、15-HETE和15-HETE-G在促进Caco-2细胞分化为肠上皮细胞中的作用。 15-HETE和15-HETE-G先前已被证明分别激活PPARgamma和PPARalpha，这两种转录因子在许多细胞类型的生长停滞和分化中具有确定的作用。 因此，实验将进一步探索15-Lox活性以及15-HETE和15-HETE-G产生在PPAR活化中的贡献。 个别PPARs在分化过程中的作用也将进行审查。 这项研究将是对15-HETE-G生物学作用的首次测试。 此外，它将评估15-Lox和PPARs在促进结直肠癌生长停滞中的作用，为癌症生物学机制提供新的见解。

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.