KLF4和SPARC在非小细胞肺癌中的表达及其相关性研究

背景与目的已有研究证实KLF4基因(Krüppel-like factor4)和富含半胱氨酸的酸性分泌蛋白(se-creted protein acidic and rich in cysteine,SPARC)与肿瘤的发生发展密切相关。本研究旨在检测KLF4和SPARC蛋白在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达,并结合临床病理特征来探讨KLF4和SPARC的临床意义及相关性。方法应用免疫组织化学方法检测89例NSCLC组织及正常肺组织中KLF4和SPARC的表达。结果 KLF4在癌旁正常肺组织阳性表达率为88.8%,NSCLC组织为42.7%(P<0.05);有、无淋巴结转移者的KLF4阳性表达率分别为31.3%和56.1%(P<0.05);KLF4的表达与肿瘤临床分期有关(P<0.05),随着临床分期等级的增加,KLF4表达呈现递减趋势。SPARC在NSCLC组织的阳性表达率为70.8%,癌旁正常肺组织为7.9%(P<0.05);低、高分化癌的SPARC阳性表达率无统计学差异(P>0.05);有、无淋巴结转移者的SPARC阳性表达率分别为81.3%和58.5%(P<0.05);其表达与肿瘤的临床分期相关(P<0.05)。KLF4和SPARC的表达均与患者的性别、年龄和肿瘤大小无关(P>0.05)。SPARC和KLF4在NSCLC中的表达呈负相关(r=-0.245,P<0.05)。结论 KLF4低表达及SPARC的过表达与NSCLC的发生及其生物学行为密切相关,可能作为NSCLC诊断及分期预后的指标。

Mechanisms simultaneously regulate smooth muscle proliferation and differentiation

Vascular smooth muscle cell （VSMC） differentiation and proliferation are two important physiological proc- esses during vascular development. The phenotypic alteration from differentiated to proliferative VSMC contrib- utes to the development of several major cardiovascular diseases including atherosclerosis, hypertension, resteno- sis after angioplasty or bypass, diabetic vascular complications, and transplantation arteriopathy. Since the VSMC phenotype in these pathological conditions resembles that of developing VSMC during embryonic development, understanding of the molecular mechanisms that control VSMC differentiation will provide fundamental insights into the pathological processes of these cardiovascular diseases. Although VSMC differentiation is usually ac- companied by an irreversible cell cycle exit, VSMC proliferation and differentiation occur concurrently during embryonic development. The molecular mechanisms simultaneously regulating these two processes, however, remain largely unknown. Our recent study demonstrates that cell division cycle 7, a key regulator of cell cycle, promotes both VSMC differentiation and proliferation through different mechanisms during the initial phase of VSMC differentiation. Conversely, Kriappel-like factor 4 appears to be a repressor for both VSMC differentia- tion and proliferation. This review attempts to highlight the novel role of cell division cycle 7 in TGF-β-induced VSMC differentiation and proliferation. The role of K141ppel-like factor 4 in suppressing these two processes will also be discussed.

KLF5对吉西他滨诱导的肺腺癌细胞凋亡的促进作用及其机制

目的研究krüppel-like factor 5基因(KLF5)的表达对吉西他滨介导的肺腺癌细胞凋亡的影响及分子机制。方法在体外培养的肺腺癌细胞H441中,分别转染KLF5表达质粒和空载体对照质粒培养68h后,加入100nmol/L的凋亡诱导药物吉西他滨处理4h,使用细胞计数和流式细胞术方法检测细胞增殖和凋亡;Western blot检测KLF5蛋白的表达,RT-PCR检测KLF5及凋亡相关基因CD95和BAX的表达;免疫荧光染色比较凋亡相关蛋白Caspase 3的表达。结果 Western blot结果证明KLF5转染成功。无吉西他滨诱导情况下,KLF5高表达对H441细胞的凋亡无显著影响,CD95和BAX基因的表达差异无统计学意义;吉西他滨诱导情况下,与对照组相比,KLF5高表达的H441细胞中凋亡细胞比例增加(P<0.05),CD95和BAX基因的表达上升(P<0.05),Caspase 3的表达上调。结论在吉西他滨诱导下,体外KLF5高表达促进肺腺癌细胞H441的凋亡。其机制可能是通过抑制细胞增殖和修复激活Caspase 3、CD95和BAX等细胞凋亡通路相关蛋白实现。