p53 suppression of arsenite-induced mitotic catastrophe is mediated by p21CIP1/WAF1

Arsenic trioxide, an acute promyelocytic leukemia chemotherapeutic, may be an efficacious treatment for other cancers. Understanding the mechanism as well as genetic and molecular characteristics associated with sensitivity to arsenite-induced cell death is key to providing effective chemotherapeutic usage of arsenite. Arsenite sensitivity correlates with deficient p53 pathways in multiple cell lines. The role of p53 in preventing arsenite-induced mitotic arrest-associated apoptosis (MAAA), a form of mitotic catastrophe, was examined in TR9-7 cells, a model cell line with p53 exogenously regulated in a tetracycline-off expression system. Arsenite activated G1 and G2 cell cycle checkpoints independently of p53, but mitotic catastrophe occurred preferentially in p53- cells. Cyclin B/CDC2(CDK1) stabilization and caspase-3 activation persisted in arsenite-treated p53- cells consistent with MAAA/mitotic catastrophe. N-Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a pan-caspase inhibitor, completely abolished arsenite-induced MAAA/mitotic catastrophe and greatly increased the mitotic index. WEE1 and p21CIP1/WAF1 inhibit cyclin B/CDC2 by CDC2 tyrosine-15 phosphorylation and direct binding, respectively. CDC2-Y15-P was transiently elevated in arsenite-treated p53+ cells but persisted in p53- cells. Arsenite induced p53-S15-P and p21CIP1/WAF1 only in p53+ cells. P21CIP1/WAF1-siRNA-treated p53+ cells were similar to p53- cells in mitotic index and cell cycle protein levels. p53-inducible proteins GADD45alpha and 14-3-3sigma are capable of inhibiting cyclin B/CDC2 but did not play a p53-dependent role in mitotic escape in TR9-7 cells. The data indicate that p53 mediates cyclin B/CDC2 inactivation and mitotic release directly via p21CIP1/WAF1 induction.     

Posttranscriptional stabilization underlies p53-independent induction of p21WAF1/CIP1/SDI1 in differentiating human leukemic cells.

p21WAF/CIP1/SDI1 is a recently identified gene expressed in cells harboring wild-type but not mutant p53 gene. It encodes a nuclear protein of 21 kD which inhibits cyclin-dependent kinase activity. Constitutive p21WAF1/CIP1/SDI1 mRNA expression was detected in neoplastic cells from patients with various hematological malignancies as well as in normal bone marrow mononuclear cells and in myeloid and lymphoid cell lines independent of their p53 status. Induced differentiation of the p53-deficient promyelocytic HL-60 cells along the monocytic lineage by phorbol ester or 1a,25 dihydroxyvitamin D3 resulted in a marked increase of both p21WAF1/CIP1/SDI1 mRNA and protein expression due to enhanced mRNA stability. Differentiation towards the granulocytic lineage by all-trans retinoic acid or dimethylsulfoxide failed to produce this effect. p21WAF1/CIP1/SDI1 is an immediate early gene since its upregulation occurred independently of de novo protein synthesis. The induction of p21WAF1/CIP1/SDI1 expression and its regulation in p53-deficient differentiating leukemic cells support the idea of an additional, p53-independent role of p21WAF1/CIP1/SDI1 in human hematopoiesis.     

AML1-ETO对p21 WAF1/CIP1启动子转录活性作用的研究

目的观察AML1-ETO融合基因对p21WAF1／CIP1基因启动子转录活性的影响，探讨AML1-ETO促进白血病发生的机制。方法构建p21WAF1／CIP1基因启动子的报告质粒，与AML1-ETO、AML1b和AML1a的表达质粒共转染非洲绿猴肾细胞系CV—1细胞，测定荧光素酶的活性，分析AML1-ETO、AML1b和AML1a对p21WAF1／CIP1基因启动子转录活性的影响。结果在CV—1细胞中，AML1-ETO对p21WAF1／CIP1基因启动子的转录具有明显的抑制作用，在pCMV5-AML1-ETO的剂量为1000ng时，p21WAF1／CIP1启动子的转录活性下降为对照组的（19±4）％，这种作用具有序列特异性和剂量依赖性；AML1b和AML1a对p21WAF1／CIP1基因启动子转录活性的抑制作用不明显，在剂量为1000ng时，p21WAF1／CIP1启动子的转录活性分别下降为对照组的（61±16）％和（594-16）％。结论AML1在与ETO形成融合基因后，其产物由于ETO蛋白能够更有效地募集转录共抑制复合物，其转录抑制活性要比AML1a和AML1b更强；外源的AML1-ETO对p21WAF1／CIP1的作用可能也与细胞系有关。     

Expression of p21(WAF1/CIP1/SDI1) and p53 in apoptotic cells in the adrenal cortex and induction by ischemia/reperfusion injury.

p21(WAF1/CIP1/SDI1), an inhibitor of cyclin-dependent kinases, is expressed at varying levels in human adrenal glands removed during surgery or organ recovery. In glands with p21 mRNA, nuclear p21 immunoreactivity, which was occasionally extensive, colocalized with p53 immunoreactivity and DNA damage, as evidenced by in situ end-labeling. Many cells showed morphological features of apoptosis when observed by fluorescent DNA dye staining and electron microscopy. This pattern was also associated with high levels of cytoplasmic heat shock protein 70. To address the question of the origin of p21 expression in some human adrenal glands, rat adrenal glands were subjected to 30 min of ischemia followed by 8 h of reperfusion. Cells with nuclear p21 and p53 appeared in the adrenal cortex together with DNA damage detected by in situ end-labeling. Nuclear p21 immunoreactivity was also produced in adrenal tissue fragments incubated at 37 degrees C in vitro. However, in this case, p21 expression was confined to the cut edge of the tissue. In contrast, p21 in human adrenal glands, as in ischemic rat glands, was within the inner regions of the cortex, supporting an origin of the protein in vivo rather than postmortem. The p53/p21 pathway of reaction to cellular injury, potentially leading to apoptosis, may play a role in tissue damage such as that resulting from ischemia/reperfusion. In the human adrenal cortex this process may be a precursor of adrenal failure.     

苯丁酸钠通过上调p21 WAF1/CIP1基因抑制白血病细胞系的细胞周期

目的研究组蛋白脱乙酰化酶(HDAC)抑制剂苯丁酸钠(PB)对白血病细胞系细胞周期的影响,探讨其分子机制.方法PB处理白血病细胞系Kasumi-1、U937和NB4细胞,分别于处理后24,48和72 h收集细胞.碘化丙锭DNA染色,流式细胞术分析细胞周期的变化.半定量逆转录-聚合酶链反应(RT-PCR)分析细胞周期相关基因p21WAF1/CIP1表达的变化.在人肾上皮细胞系293T细胞用荧光素酶报告基因分析PB对p21WAF1/CIP1基因启动子活性的影响.结果PB可以抑制Kasumi-1、U937和NB4细胞的细胞周期,作用呈时间和剂量依赖关系.3 mmol/L PB作用72 h,分别使Kasumi-1、U937和NB4细胞的G0/G1期细胞比例增加42.03%、44.36%和26.82%,S期细胞比例减少31.86%、38.91%和26.77%.PB使Kasumi-1、U937和NB4细胞p21WAF1/CIP1表达增高.PB处理后,p21WAF1/CIP1的表达水平较处理前增高(2.06±0.27),(2.78±0.40)和(1.78±0.20)倍.PB可以上调p21WAF1/CIP1启动子的转录活性,且呈剂量依赖关系.3 mmol/L PB处理48 h使转录活性增高(5.74±0.93)倍.PB上调p21WAF1/CIP1启动子转录活性主要是依赖于转录起始位点上游101 bp的序列.结论PB可以抑制白血病细胞系的细胞周期,这种作用可能是通过上调细胞周期相关基因p21WAF1/CIP1的表达实现的.     

血管平滑肌细胞表型改变与肿瘤抑制基因p21WAF1和p53的关系

目的增殖表型血管平滑肌细胞中肿瘤抑制基因p21WAF1基因和p53基因表达可能具有对抗血管平滑肌细胞的增殖能力,观察血管平滑肌细胞表型变化与肿瘤抑制基因p21WAF1和p53的关系.方法实验于2003-09/10哈尔滨医科大学医学遗传学研究室完成.应用胶原酶消化法建立大鼠原代培养血管平滑肌细胞,去血清诱导体外培养血管平滑肌细胞分化.流式细胞分析检测不同表型血管平滑肌细胞增殖能力,反转录-聚合酶链反应和蛋白质印迹分析方法检测血管平滑肌细胞分化相关基因平滑肌特异性α-肌动蛋白和calponin表达变化,反转录-聚合酶链反应和蛋白质印迹杂交方法检测p21 WAF1和p53基因表达变化.结果去血清培养后,原代培养大鼠血管平滑肌细胞增殖能力下降,DNA合成前期细胞明显增加[(48.38±2.35)%],细胞分化基因平滑肌特异性α-肌动蛋白和calponin明显表达.肿瘤抑制基因p21WAF1和p53表达下降.在200 g/L血清培养后,大鼠血管平滑肌细胞增殖旺盛,DNA合成前期细胞相对较少[(28.80±1.58)%],细胞分化相关基因平滑肌特异性肌动蛋白和calponin表达明显下调,肿瘤抑制基因p21 WAF1和p53表达显著增加.结论肿瘤抑制基因表达与血管平滑肌细胞表型状态密切相关.提示某些病理性增殖过程中肿瘤抑制基因的大量表达可能与其对抗细胞增殖的功能相关,并可能在血管平滑肌细胞由合成表型逆转为分化表型的分子调控中发挥作用.     

Roles of the Tumor Suppressor p53 and the Cyclin-dependent Kinase Inhibitor p21WAF1/CIP1 in Receptor-mediated Apoptosis of WEHI 231 B Lymphoma Cells

Treatment of WEHI 231 immature B lymphoma cells with an antibody against their surface immunoglobulin M (anti-IgM) induces apoptosis and has been studied extensively as a model of self-induced B cell tolerance. Since the tumor suppressor protein p53 has been implicated in apoptosis in a large number of cell types and has been found to be mutated in a variety of B cell tumors, here we sought to determine whether p53 and the p53 target gene cyclin-dependent kinase inhibitor p21^WAF1/CIP1 were involved in anti-IgM–induced cell death. Anti-IgM treatment of WEHI 231 cells increased expression of p53 and p21 protein levels. Ectopic expression of wild-type p53 in WEHI 231 cells induced both p21 expression and apoptosis. Ectopic expression of p21 similarly induced apoptosis. Rescue of WEHI 231 cells from apoptosis by costimulation with CD40 ligand ablated the increase in p21 expression. Lastly, a significant decrease in anti-IgM–mediated apoptosis was seen upon downregulation of endogenous p53 activity by expression of a dominant-negative p53 protein or upon microinjection of an antisense p21 expression vector or antibody. Taken together, the above data demonstrate important roles for p53 and p21 proteins in receptor-mediated apoptosis of WEHI 231 B cells.     

人脑胶质瘤组织中P21WAF/CIP1的异常表达及其病理学意义

目的探讨人脑胶质瘤组织P21WAF/CIP1的表达水平与胶质瘤恶性度的关系。方法免疫组化方法检测人脑胶质瘤标本41例,并对其表达水平进行评价。结果P21WAF/CIP1表达水平随胶质瘤恶性程度的升高呈下降趋势,但与组织学分级无相关性,全部受检标本P21WAF/CIP1染色强度无差异。结论胶质瘤组织P21WAF/CIP1表达呈异质性,与胶质瘤分级无相关性,但可参与胶质瘤的发生、发展。     

Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21(WAF1/CIP1) expression with rapamycin

HER2 overexpression, which confers resistance to various therapeutic regimens, correlates with a poor clinical prognosis. In this study, we showed that luteolin, a naturally occurring flavonoid, is a potent stimulator of HER2 degradation. Luteolin effectively inhibited cell proliferation and induced apoptosis in HER2-overexpressing cancer cells. Furthermore, we found that low doses of luteolin up-regulated p21 expression and high doses of luteolin down-regulated its expression. Examination of the Akt/mammalian target of rapamycin (mTOR) signaling revealed that this signaling was only transiently inhibited by low doses of luteolin, which suggested that the inability to cause sustained Akt/mTOR inhibition may contribute to p21 induction and provide a survival advantage to HER2-overexpressing cancer cells. To test this hypothesis, we showed that the combined use of luteolin and mTOR inhibitor rapamycin prevented low doses of luteolin from inducing p21 expression, and HER2-overexpressing cancer cells would be sensitized toward luteolin-induced apoptosis. In addition, p21 small interfering RNA also increased the luteolin-induced cell death. In nude mice with xenografted SKOV3.ip1-induced tumors, luteolin significantly inhibited HER2 expression and tumor growth in a dose-dependent manner, and rapamycin further enhanced the effect of luteolin with a concomitant p21 inhibition. These results reveal an intriguing finding that suppressing p21 expression might have therapeutic implications and further suggest that combination of mTOR inhibitors may be a promising strategy to help increase the efficacy of preventive or therapeutic compounds against HER2-overexpressing tumors.     

Induction of p21WAF1/CIP1/SDI1 in kidney tubule cells affects the course of cisplatin-induced acute renal failure.

The p21 protein is found in the nucleus of most cells at low levels and is induced to elevated levels after DNA damage, causing cell-cycle arrest. We have reported that p21 mRNA is rapidly induced to high levels in murine kidney after acute renal failure. The function(s) in the kidney of p21 induction in cisplatin-induced acute renal failure was studied with mice that are homozygous for a p21 gene deletion. After drug administration, as compared with their wild-type littermates, p21(-/-) mice display a more rapid onset of the physiologic signs of acute renal failure, develop more severe morphologic damage, and have a higher mortality. Therefore, the induction of p21 after cisplatin administration is a protective event for kidney cells. Using both bromodeoxyuridine incorporation and nuclear proliferating cell nuclear antigen detection, we found that cisplatin administration caused kidney cells to start entering the cell-cycle. However, cell-cycle progression is inhibited in wild-type mice, whereas kidney cells in the p21(-/-) mice progress into S-phase. We propose that p21 protects kidneys damaged by cisplatin by preventing DNA-damaged cells from entering the cell-cycle, which would otherwise result in death from either apoptosis or necrosis.     

Coexpression of p21(WAF1/CIP1) in adenovirus vector transfected human primary hepatocytes prevents apoptosis resulting in improved transgene expression

Replication-deficient adenovirus (Ad vector) is one of the most effective gene transfer systems. However, its employment in human gene therapy trials is hampered by Ad vector associated cytotoxicity and induction of apoptosis of the infected cells. Here, we identify one underlying mechanism as uncoupling of S phase and mitosis of the cell cycle leading to apoptosis and decline of transgene expression. Moreover, we demonstrate a strategy to avoid Ad vector associated cytotoxicity and induction of apoptosis in human primary hepatocytes by coinfection of Ad vector carrying the cDNA of choice and the cell cycle regulator p21(WAF1/CIP1) (p21). In addition, animal experiments were performed using Ad vector directed coexpression of p21 and human alpha 1-antitrypsin. As serum analysis of alpha 1-antitrypsin after Ad vector mediated gene transfer to the liver of mice revealed, this strategy resulted also in the improvement of transgene expression by two orders of magnitude. These data suggest that coexpression of p21 and Ad vector carrying a therapeutic gene may be a promising strategy to avoid cytotoxicity and induction of apoptosis leading to improved safety in human gene therapy.     

The cyclin-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21WAF1/CIP1 expression and maturation while reciprocally potentiating apoptosis in human leukemia cells

Interactions between the cyclin-dependent kinase inhibitor flavopiridol (FP) and the histone deacetylase inhibitor sodium butyrate (SB) have been examined in human leukemia cells (U937) in relation to differentiation and apoptosis. Whereas 1 mM of SB or 100 nM of FP minimally induced apoptosis (4% and 10%, respectively) at 24 h, simultaneous exposure of U937 cells to these agents dramatically increased cell death (e.g., approximately 60%), reflected by both morphological and Annexin/propidium iodide-staining features, procaspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Similar interactions were observed in human promyelocytic (HL-60), B-lymphoblastic (Raji), and T-lymphoblastic (Jurkat) leukemia cells. Coadministration of FP opposed SB-mediated accumulation of cells in G0G1 and differentiation, reflected by reduced CD11b expression, but instead dramatically increased procaspase-3, procaspase-8, Bid, and poly(ADP-ribose) polymerase cleavage, as well as mitochondrial damage (e.g., loss of mitochondrial membrane potential and cytochrome c release). FP also blocked SB-related p21WAF1-CIP1 induction through a caspase-independent mechanism and triggered the caspase-mediated cleavage of p27KIP1 and retinoblastoma protein. The latter event was accompanied by a marked reduction in retinoblastoma protein/E2F1 complex formation. However, FP did not modify the extent of SB-associated acetylation of histones H3 and H4. Treatment of cells with FP/SB also resulted in the caspase-mediated cleavage of Bcl-2 and caspase-independent down-regulation of Mcl-1. Levels of cyclins A, D1, and E, and X-linked inhibitor of apoptosis also declined in SB/FP-treated cells. Finally, FP/SB coexposure potently induced apoptosis in two primary acute myelogenous leukemia samples. Together, these findings demonstrate that FP, when combined with SB, induces multiple perturbations in cell cycle and apoptosis regulatory proteins, which oppose leukemic cell differentiation but instead promote mitochondrial damage and apoptosis.     

P21WAF1/CIP1和细胞周期蛋白E在脂溢性角化病中的表达及意义

目的研究脂溢性角化病皮损组织中P21WAF1/CIP1和细胞周期蛋白E(Cyclin E)表达和意义.方法采用免疫组织化学SP法对45例脂溢性角化病皮损组织及20例正常皮肤组织中P21WAF1/CIP1和Cyclin E表达进行检测.结果脂溢性角化病皮损组织P21WAF1/CIP1和Cyclin E 阳性表达率及表达强度均明显高于正常皮肤组织(P<0.05);P21WAF1/CIP1和Cyclin E 表达与患者年龄、性别、肿瘤组织学类型均不相关(P>0.05).结论P21WAF1/CIP1和Cyclin E过度表达与脂溢性角化病的发生发展密切相关.     

鼻腔、鼻窦鳞状细胞癌中p53、p21蛋白表达及HPV16/18感染的意义

目的探讨p53和p21的表达及HPV感染在鼻腔、鼻窦鳞状细胞癌（简称鼻鳞癌）中的意义。方法用EnVision免疫组化二步法检测28例鼻鳞癌和24例鼻息肉中p53和p21的表达情况,并用原位杂交方法检测其HPV16／18的感染情况。结果鼻鳞癌组中p53的阳性表达率为64．29％,鼻息肉组中053未见表达,两组比较差异极显著（P〈0．01）;而p21的阳性表达率在鼻鳞癌组和鼻息肉组间差异不显著;鼻鳞癌组肝V16／18检出率为78．57％,鼻息肉组HPV16／18检出率为0,两组比较差异极显著（P〈0．01）。结论v53基因突变以及HPV感染与鼻鳞癌的发生、发展可能有一定的相关性。     

p21waf1和p53及增殖细胞核抗原在肺癌组织中的表达

背景：细胞周期调控蛋白水平及其相互关系是良恶性细胞增殖的主要区别标准。目的：了解肺癌组织p21waf1和p53及增殖细胞核抗原蛋白表达情况。设计：病例对照。单位：武汉大学人民医院呼吸内科。对象：来自1996-10／1999-05武汉大学人民医院保存的胸外科手术和纤维支气管镜活检组织石蜡包埋标本135块。其中肺癌76块，肺良性疾病59块。肺癌组中患者男56例，女20例；年龄18-74岁。肺良性疾病组中患者男42例，女17例；年龄16-70岁。方法：用磷酸盐缓冲液代替一抗作为阴性对照。染色步骤按试剂盒说明进行。p21waf1采用高温高压修复法，p53采用微波修复法，增殖细胞核抗原无需抗原修复。①p21waf1和p53阳性染色判断标准：计数连续5个高倍镜视野中胞核染成黄褐色的阳性细胞所占比例，以≥10％为阳性，〈10％为阴性。②增殖细胞核抗原阳性判断标准：连续观察5个高倍镜视野，每个高倍镜视野计数100个细胞中胞核染成黄褐色的阳性细胞所占比例，取其平均值，记为增殖细胞核抗原标记指数。主要观察指标：p21waf1和p53及增殖细胞核抗原蛋白表达水平。结果：①肺癌组织p21waf1和p53蛋白表达阳性率分别为75％（57／76）和47％（36／76），增殖细胞核抗原标记指数显著高于肺良性疾病组织（0．44&;#177;0．32，0．09&;#177;0．14）。②肺癌组织p21waf1和p53及增殖细胞核抗原蛋白表达与肺癌临床分期及细胞分化程度无关。③肺鳞癌增殖细胞核抗原标记指数明显高于小细胞肺癌（0．51&;#177;0．33，0．30&;#177;0.36）。④肺癌组织p21waf1和p53表达与增殖细胞核抗原无关，而肺良性疾病组织p21waf1表达与增殖细胞核抗原有相关性。结论：肺癌组织p21waf1与p53蛋白表达明显上调，肺癌细胞增殖程度高。肺鳞癌细胞DNA损伤修复能力可能高于小细胞肺癌。肺良性疾病细胞增殖过程中，p21waf1和p53及增殖细胞核抗原3种蛋白作用协调。而肺癌细胞中3种蛋白作用不协调。     

p21waf1和p53及增殖细胞核抗原在肺癌组织中的表达

背景细胞周期调控蛋白水平及其相互关系是良恶性细胞增殖的主要区别标准.目的了解肺癌组织p21waf1和p53及增殖细胞核抗原蛋白表达情况.设计病例对照.单位武汉大学人民医院呼吸内科.对象来自1996-10/1999-05武汉大学人民医院保存的胸外科手术和纤维支气管镜活检组织石蜡包埋标本135块.其中肺癌76块,肺良性疾病59块.肺癌组中患者男56例,女20例;年龄18～74岁.肺良性疾病组中患者男42例,女17例;年龄16～70岁.方法用磷酸盐缓冲液代替一抗作为阴性对照.染色步骤按试剂盒说明进行.p21waf1采用高温高压修复法,p53采用微波修复法,增殖细胞核抗原无需抗原修复.①p21waf1和p53阳性染色判断标准计数连续5个高倍镜视野中胞核染成黄褐色的阳性细胞所占比例,以≥10%为阳性,＜10%为阴性.②增殖细胞核抗原阳性判断标准连续观察5个高倍镜视野,每个高倍镜视野计数100个细胞中胞核染成黄褐色的阳性细胞所占比例,取其平均值,记为增殖细胞核抗原标记指数.主要观察指标p21waf1和p53及增殖细胞核抗原蛋白表达水平.结果①肺癌组织p21waf1和p53蛋白表达阳性率分别为75%(57/76)和47%(36/76),增殖细胞核抗原标记指数显著高于肺良性疾病组织(0.44±0.32,0.09±0.14).②肺癌组织p21waf1和p53及增殖细胞核抗原蛋白表达与肺癌临床分期及细胞分化程度无关.③肺鳞癌增殖细胞核抗原标记指数明显高于小细胞肺癌(0.51±0.33,0.30±0.36).④肺癌组织p21waf1和p53表达与增殖细胞核抗原无关,而肺良性疾病组织p21waf1表达与增殖细胞核抗原有相关性.结论肺癌组织p21waf1与p53蛋白表达明显上调,肺癌细胞增殖程度高.肺鳞癌细胞DNA损伤修复能力可能高于小细胞肺癌.肺良性疾病细胞增殖过程中,p21waf1和p53及增殖细胞核抗原3种蛋白作用协调,而肺癌细胞中3种蛋白作用不协调.     

高功率微波对兔眼晶状体上皮细胞P21WAFl及Cyclin E表达的影响

目的 观察高功率微波(high power microwave,HPM)对实验动物兔眼晶状体上皮细胞P^21WAF1、Cyclin E表达水平的影响,以探讨防护HPM眼损伤的机理及方法。方法 采用功率密度为800mW／cm^2的微波持续照射青紫兰兔眼组织20min,并于微波照射后30d,90d,180d及360d时应用免疫组化、原位杂交及图像分析技术对兔眼晶状体上皮细胞P^21WAF1、Cyclin E蛋白及其mRNA表达水平进行检测。结果 HPM照射可影响晶状体上皮细胞的正常增殖过程;当HPM照射后30d时,P^21WAF1表达明显升高,对细胞增殖周期抑制作用增强;Cyclin E表达则明显降低,其正性调节细胞生长作用减弱;当HPM照射后90,180及360d时,微波照射组上述各指标与对照组比较,差异均无显著性意义,而且各项指标的mRNA表达均与其蛋白表达同步且一致。结论 HPM照射可干扰细胞正常的牛长增殖周期进程,而晶状体上皮细胞增殖异常可能是导致白内障的重要原因之一。     

细胞增殖抑制基因、p21WAF1蛋白在非小细胞肺癌组织中的表达及其意义

目的 探讨细胞增殖抑制基因(HSG/Mfn2)、p21WAF1蛋白在非小细胞肺癌中的表达及相关性.方法 采用免疫组化SP法检测92例非小细胞肺癌中HSG/Mfn2、p21WAF1蛋白的表达.结果 HSG/Mfn2在肺鳞癌、腺癌、非癌肺组织中吸光度值分别为15.06±2.73、12、21±2.96、10.36±3.60,差异有统计学意义(P<0.05),并与肺癌分化程度有关.p21WAF1蛋白在肺鳞癌、腺癌、非癌肺组织中吸光度值分别为3.16±0.98、3.44±0.22、0.06±0.32,肺鳞癌和腺癌组织与非癌组织比较差异均有统计学意义(均P<0.05),与分化程度、淋巴结转移有关.结论 HSG/Mfn2,p21WAF1蛋白与肺癌发生、发展密切相关.二者在肺癌组织中的表达呈正相关.