权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of gene therapy on lung cancer with regulation of expression and metabolism of cell cycle regulator p27Kip1

细胞周期调节因子p27Kip1表达和代谢调控肺癌基因治疗进展

基本信息

批准号：
13557054
负责人：
MATSUSE Takeshi
金额：
$ 6.21万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557054/
关键词：
cell cycle regulator gene therapy lung cancer p27Kip 1

项目摘要

1.Regulation of apoptosis and necrosis of lung cancer cells by controlling the expression level of p27Kip1.We investigated the role of p27Kip1 on cell viability in A549 lung adenocarcinoma cells. p27Kip1 overexpression with adenovirus vector reduced viral-induced apoptosis, and depletion of p27Kip1 with siRNA induced apoptosis. It was also speculated that cytoplasmic portion of p27Kip1 has this protective capacity against apoptosis.2.The mechanism to regulate the intracellular localization of p27Kip1Next, we checked the mechanism to regulate the intracellular localization of p27Kip1. Forced expression of p27Kip1 cDNA with substitution of S10, T157, and T198 to glutamate (phospho-mimetic) induced its cytoplasmic localization.3.The role of p27Kip1 on cell cycle regulation in lung cancer cells.We regulated p27Kip1 exptession level upward with adenovector and downward with the siRNA method in A549 cells. Although overexpression of p27Kip1 reduced cell cycle progression, its removal did not change cell cycle status.4.The role of p27Kip1 on viability under the state of nutritional deficiency in lung cancer cellsWe investigated the role of p27Kip1 on viability under the state of nutritional deficiency (amino acid or glucose) in A549 lung adenocarcinoma cells. It was supposed that amino acid or glucose deprivation induced cell cycle arrest and cell death, part of which is thought to be rescued by the existence of cytoplasmic p27Kip1.

1.通过调控p27 Kip 1的表达水平调控肺癌细胞凋亡和坏死。用腺病毒载体过表达p27Kip1可减少病毒诱导的细胞凋亡，而用siRNA去除p27Kip1可诱导细胞凋亡。推测p27Kip1的胞浆部分具有这种抗凋亡的保护作用。2. p27Kip1的胞内定位调节机制p27Kip1基因在肺癌细胞中的表达研究：用腺病毒载体上调p27Kip1基因在A549细胞中的表达，用siRNA下调p27Kip1基因在A549细胞中的表达。p27Kip1的过表达虽然降低了细胞周期进程，但其去除并不改变细胞周期状态。4. p27Kip1对营养缺乏状态下肺癌细胞活力的影响我们研究了p27Kip1对营养缺乏（氨基酸或葡萄糖）状态下A549肺腺癌细胞活力的影响。据推测，氨基酸或葡萄糖剥夺诱导细胞周期停滞和细胞死亡，其中一部分被认为是由细胞质p27 Kip1的存在拯救。