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Enhancer of zeste homolog 2 ( EZH2 ) is a key epigenetic regulator that catalyzes the trimethyla-tion of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associat-ed factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 ( PRC2 ) . Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients pre-dicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acety-lation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.
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女性肺腺癌易感性机制的研究进展
肺癌是全球发病率较高的严重危害人类健康的恶性肿瘤.20世纪90年代西方发达国家男性肺癌的发病率和病死率开始缓慢下降,而女性肺癌的发病率和病死率仍在持续上升[1].大量研究结果证实,吸烟为肺癌发病的主要原因,与鳞癌的发生有关.而女性无论吸烟与否均以腺癌居多,这提示女性本身可能存在某些分子生物学的易感因素,现将有关研究综述如下.
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Objective: To clone multidrug resistance (MDR) related genes in lung adenocarcinoma cell lines. Methods: The differentially expressed cDNA fragments between A549 and A549DDP cells were analyzed by mRNA differential display PCR(DD RT-PCR). The fragments thus obtained were further analyzed by DNA sequencing and Northern blotting. Results: Three differentially expressed cDNA fragments were obtained and confirmed by Northern blot. Sequence analysis revealed that two of them were novel and one was 100% identical with ICE gene. Conclusion: Analyzing differentially expressed fragment between A549 and A549DDP cells may be helpful for finding new MDR related genes. The drug resistance of A549DDP cells may be related to the inhibition or down-regulation of ICE gene.
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伴有甲胎蛋白升高的肺腺癌一例
1 临床资料患者,男性,65岁,2006年4月体检发现甲胎蛋白(AFP)升高,并呈进行性升高趋势,4月29日AFP为263.3μg/L;腹部CT检查未见肝脏占位.患者否认肝病史,各型肝炎相关指标检测也均为阴性.5月29日在上海某医院行肝动脉化疗栓塞术(TACE),术中未见肝内异常,注入羟基喜树碱10 mg+表柔比星20 mg+脱氧氟脲苷500 mg.6月30日复查AFP为383 μg/L.此后未再行进一步的治疗措施.7月胸片及胸部CT均提示右下叶后基底段阴影;CEA、CA125等肿瘤标志物均正常,考虑肺部感染可能,予阿奇霉素、林可霉素等抗感染治疗,后定期随访.
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低分化肺腺癌左上臂及背部肌内转移1例
肺癌晚期可出现各个不同脏器的转移而引起相应的症状,常常给患者带来极大的痛苦,甚至威胁到生命.肺癌转移主要以直接蔓延和淋巴结转移为主,晚期可发生血行转移.首发症状为软组织转移较少见,现对新疆医科大学第一附属医院诊治的1例低分化肺腺癌左上臂及背部肌内转移的病例报道如下.