NUTRITION AND PROTEIN METABOLISM IN TUMOR AND HOST

描述：该项目的重点是两个关键的发现：（1）鱼油和 omega-3脂肪酸延长了DNA复制的持续时间， 增殖的细胞系，这种作用与细胞增殖的变化有关。 DNA复制起点的位置;和（2）PDGF受体mRNA的水平 在用鱼油处理的成纤维细胞中显著增加。 博士 Istfan假说认为脂肪酸会影响 通过改变细胞核的结构来组织复制起点 膜的 后者被认为会影响到组织结构， 核基质与DNA复制起点有关， 特异性附着（支架附着区，SAR）。 可选择地， 核膜流动性的程度，脂肪酸的功能 组合物，影响核孔复合物，从而改变核孔复合物的动力学。 核质运输 伊斯特凡医生会检测 在细胞培养物和无细胞培养物中， 爪蟾复制系统。 膜流动性与细胞增殖 动力学将与核膜脂肪酸、核膜 孔功能和核基质组织通过研究SAR和 温度敏感的核基质蛋白的共聚焦显微镜。 博士 Istfan还假设PDGF受体调节补偿了 鱼油处理的成纤维细胞中增殖信号降低。 的研究 检查鱼油处理的S期延长与 将启动成纤维细胞和PDGF受体的调节。 的 该受体和G1/S细胞周期蛋白在介导 将检查G1相位调节的补偿变化。

DESCRIPTION: This project is focused on two key findings: (1) Fish oil and omega-3 fatty acids prolong the duration of DNA replication in several proliferating cell lines and this effect is associated with a change in the location of a DNA replication origin; and (2) Levels of PDGF receptor mRNA are significantly increased in fibroblasts treated with fish oil. Dr. Istfan hypothesis is that fatty acids influence the spatial and temporal organization of replication origins by altering the structure of the nuclear membrane. The latter is thought to impact on the organization of the nuclear matrix which has been related to DNA replication origins through specific attachments (scaffold attachment regions, SARs). Alternatively, the degree of nuclear membrane fluidity, a function of fatty acid composition, affects the nuclear pore complex, thus altering the kinetics of nucleocytoplasmic trafficking. Dr. Istfan will test the extent of fatty acid incorporation into nuclear membranes in cell cultures and the cell-free Xenopus replicating system. Membrane fluidity and cell proliferation kinetics will be related to nuclear membrane fatty acids, nuclear membrane pore function, and nuclear matrix organization through studies of SARs and temperature-sensitive nuclear matrix proteins by confocal microscopy. Dr. Istfan also postulates that PDGF receptor regulation compensates for a reduced proliferation signal in fish oil-treated fibroblasts. Studies that examine the relationship between S phase lengthening in fish oil treated fibroblasts and regulation of the PDGF receptor will be initiated. The functional role(s) of this receptor and those of G1/S cyclins in mediating compensatory changes in G1 phase regulation will be examined.