LASS2/TMSG-1诱导人肺癌细胞发生凋亡的机制研究

LASS2/TMSG-1（homo sapiens longevity assurance homologue 2 of yeast LAG1/ tumor metastasis suppressor gene-1）is a new tumor metastasis suppressor gene and closely related with the invasion、metastasis、growth and apoptosis of tumor. However, only a few studies is on the mechanism of the gene in the procedure of tumor cell apoptosis. This research project intends to study whether LASS2 / TMSG-1 gene induces tumor cell apoptosis through regulating V-ATPase (vacuole ATPase) to activate mitochondrial apoptosis pathway by gene silencing, gene transferring and testing of the mitochondrial membrane potential; study whether LASS2/TMSG-1 gene participates in the apoptosis of tumor cells through synthetic ceramide by detecting ceramide synthesis ability of tumor cells through high performance liquid chromatography-fluorescence detecting(HPLC-FLD) and the study on the mechanism of apoptosis; and look for the conduction pathway among the apoptotic signals related to LASS2 / TMSG-1 gene by using gene chips technology. Thus we will have a more comprehensive study on the mechanism promoting the apoptosis of LASS2/TMSG-1 gene, so as to search for genes and therapeutic targets associated with lung cancer and provide theoretical basis for gene therapy of lung cancer. In particular, this project will apply LASS2/TMSG-1 to detect a large number of clinical lung cancer specimens, and this will provide a large number of clinical and pathological basis for judging the prognosis、growth and apoptosis of lung cancers.

LASS2/TMSG-1基因是一种新的肿瘤转移抑制基因，与肿瘤的侵袭转移、生长及凋亡密切相关。目前，人们对其参与诱导肿瘤细胞凋亡的机制研究较少。本课题拟通过基因沉默等方法来研究LASS2/TMSG-1基因是否通过调控V-ATPase（液泡型ATP酶）激活依赖线粒体凋亡途径从而诱导肿瘤细胞发生凋亡；通过高效液相质谱-荧光检测器法检测肿瘤细胞合成神经酰胺的能力，来探究LASS2/TMSG-1是否通过合成神经酰胺来参与肿瘤细胞的凋亡，并对其凋亡机制进行初步研究；本课题并利用基因芯片技术来寻找与LASS2/TMSG-1相关的凋亡信号传导通路，从而全面地研究LASS2/TMSG-1基因的促肿瘤凋亡机制，进而寻找与肺癌相关的基因和治疗靶点，为肺癌的基因治疗提供理论依据。尤其是本课题将LASS2/TMSG-1应用到了大量临床肺癌标本中的检测，从而为判断肿瘤生长、凋亡及预后提供了大量的临床病理依据。