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1.
Expressions of Cell Cycle Regulators in Human Colorectal Cancer Cell Lines   总被引:3,自引:0,他引:3  
To study the altered mechanisms of cell cycle regulation in colorectal cancer, the expressions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, p53 and retinoblastoma (Rb) protein were analyzed by western blotting in a series of human colorectal cancer cell lines. The colorectal cancer cell lines exhibited various expression patterns of cell cycle regulators, which may reflect differences in the biological characteristics of cancer cells and in the genetic backgrounds of carcinogenesis. A correlation was found between p53 gene alteration and p21 expression, suggesting that p53 gene mutation usually suppresses p21 expression, though p21 expression could be induced via both ap53 -dependent and a p53 -independent pathway in colorectal cancer. None of the cell lines studied expressed p16 protein, suggesting that inactivation of p16 may be a common alteration in colorectal cancer. Moreover, all the D-type cyclins, especially D2 and D3, were expressed at a high level in most of the cell lines. Loss of p16 expression and increased expression of D-type cyclins promote CDK-mediated Rb phosphorylation. All of the colorectal cancer cell lines studied herein expressed Rb protein, but the growth-suppressive properties of Rb may be inactivated by the loss of p16 expression and increased expressions of D-type cyclins. In view of the pivotal role of Rb in cell cycle regulation, loss of p16 expression and overexpression of D-type cyclins may be critical alterations in colorectal cancer.  相似文献   

2.
Cyclin A、CDK2基因在非小细胞肺癌中的表达及其意义   总被引:1,自引:0,他引:1  
目的研究细胞周期素A(Cyclin A)和细胞周期素依赖性激酶2(cyclin—dependent kinases,CDK2)基因在非小细胞肺癌(non—small—cell lung cancer,NSCLC)组织中的表达及其相互关系,探讨其对NSCLC发生、发展、淋巴结转移及预后的影响。方法采用免疫组织化学二步法检测40例NSCLC(伴淋巴结转移21例,不伴淋巴结转移19例),11例支气管黏膜上皮增生或不典型增生,9例淋巴结转移癌组织中Cyclin A、CDK2蛋白的表达,并随访40例NSCLC患者3年生存期。结果在支气管黏膜上皮增生或不典型增生,不伴淋巴结转移的NSCLC,伴淋巴结转移的NSCLC,淋巴结转移癌组织中,Cyclin A蛋白的阳性表达率分别为9.09%(1/11),31.58%(6/19),80.95%(17/21),66.67%(6/9);CDK2蛋白的阳性表达率分别为9.09%(1/11),36.84%(7/19),76.19%(16/21),77.7896(7/9);不伴淋巴结转移的NSCLC组织中的Cyclin A、CDK2蛋白阳性表达率分别与伴淋巴结转移NSCLC组织、淋巴结转移癌组织的Cyclin A、CDK2蛋白阳性表达率比较,差异均有显著性(P均〈0.05)。23例Cyclin A蛋白表达阳性患者3年生存率为21.74%(5/23),17例表达阴性患者3年生存率为58.82%(10/17),两者比较有显著性差异(P〈0.05);23例CDK2蛋白表达阳性息者3年生存率为17.39%(4/23),17例表达阴性患者3年生存率为64.71%(11/17),两者比较有显著性差异(P〈0.05)。NSCLC中Cyclin A与CDK2蛋白表达呈正相关(x^2=19.22,P〈0.001,列联系数Pearson=0.570)。结论在NSCLC发生、演进、浸润、淋巴结转移过程中Cyclin A、CDK2起正调控作用,NSCLC组织中Cyclin A、CDK2表达上调可作为判断NSCLC预后不良的参考指标。  相似文献   

3.
The main cause of the cellular malignant proliferation is the disorder of cell division and growth. The alterations of proteins and genes that involved in this process correlate closely with the occurrence and vicious phenotype of neoplasm. Cyclin D1 and cyclin-dependent kinase 4 (CDK4) regulatory proteins in G1 phase have a direct bearing on carcinogenesis. Presently, gene amplification, overexpression, chromosome inversion andtranslocation of cyclin D1 and CDK4 have been discovered in ma…  相似文献   

4.
Background: HLA-G, a major histocompatibility complex of non-classical class Ib, plays a key role in thedevelopment of the primary tumors to metastatic stages. The aim of this study was to investigate HLA-G expression in oralsquamous cell carcinomas and its relationship with clinicopathological factors. Methods: After immunohistochemicalstaining for HLA-G with 63 formalin fixed and paraffin embedded blocks (33 oral squamous cell carcinoma and 30 normaloral mucosa samples), staining intensity, percentage of stained cells and final immunoreactivity score were evaluated,along with other variables. Results: Staining intensity, percentage of stained cells and final immunoreactivity scores inoral squamous cell carcinomas were higher than those in normal oral mucosa (all P=0.001). The staining intensity inthe parenchyma of squamous cell carcinoma cells was significantly associated with the clinical tumor stage (P=0.022)and the group with lymphatic metastasis exhibited a higher staining percentage (P=0.026). Staining intensity andimmunoreactivity score (IRS) exhibited a significant but inverse correlation with survival rate (P=0.004 and P=0.018,respectively) and a significant direct relationship with clinical stage (P=0.001 and P=0.001). Conclusion: The resultssupported a role of HLA-G in development of oral squamous cell carcinomas and metastasis to lymph nodes. It mightbe useful in molecular-targeted therapy.  相似文献   

5.
目的:从细胞周期调控的角度来探讨口腔鳞状细胞癌(OSCC)的发生、发展及预后和p27、cyclin D1和CDK4的关系。方法:采用免疫组织化学方法,检测了50例口腔鳞状细胞癌及10例正常口腔粘膜中p27、cyclinD1和CDK4蛋白表达的水平,然后用Spearman 相关分析检查它们与临床病理学指标的关系以及它们三者之间的相关关系,用Kaplan-Meier方法绘制生存曲线并进行生存分析,Cox比例风险模型作预后分析。结果:1)p27在所有正常口腔粘膜上皮均呈现高表达,而在口腔鳞状细胞癌组织表达降低,p27的低表达与临床分期,淋巴结转移有显著性相关关系,cyclin D1和CDK4在正常粘膜上皮呈现低水平表达,在口腔钙状细胞癌组织中过表达。2)cyclinD1和CDK4在正常粘膜上皮呈现低水平表达,在口腔鳞状细胞癌组织中过表达.2)cyclin D1的表达与CDK4呈正相关(r=0.442,P=0.001);p27与CDK4的表达呈负相关(r=-0.384,P=0.006).3)Kaplan-Meier生存分析显示p27高表达组( )的各期的生存均高于低表达组(-),cyclin D1染色( )组的生存率低于(-)组。4)Cox比例风险模型分析结果显示p27蛋白表达水平,cyclinD1蛋白表达水平,淋巴结转移和临床分期分别是口腔鳞状细胞癌的独立预后指标。结论:口腔鳞状细胞癌组织中,p27,cyclin D1和CDK4蛋白的异常表达说明它们均参与了口腔鳞状细胞癌的发生发展,且在这一过程中三者之间存在相互协同与制约关系。在临床应用中有可能将p27和cyclin D1蛋白的表达程度作为判断口腔鳞状癌患者预后的指标。  相似文献   

6.
颌骨骨肉瘤中cyclinD1和CDK4的表达及其意义   总被引:1,自引:0,他引:1  
分析细胞周期素D1(cyclinD1)和细胞周期素依赖激酶4(CDK4)在颌骨骨肉瘤中的表达及意义。方法采用免疫组化ABC法检测cyclinD1和CDK4在20例颌骨骨肉瘤和8例骨软骨瘤中的表达。结果骨肉瘤中cyclinD1和CDK4的阳性率表达率分别为65.00%(13/20)和60.00%(12/20),两者的阳性表达存在正相关(γS=0.48,P〈0.05);而它们在骨软骨瘤中的阳性率均为1  相似文献   

7.
 目的 观察cyclin E 的高表达对乳腺癌细胞MCF 7 生长及周期的影响。方法 构建cyclin EcDNA真核表达载体并采用lipofectAMINE 转染方法将其导入MCF 7 细胞,获得稳定表达cyclin E的细胞系。通过对细胞生长曲线绘制、3H TdR测定及细胞周期分布等的分析,观察其对细胞生长、增殖的影响。结果 cyclin E的高表达可以使细胞的生长速度加快( 约为对照1-52 倍) 及DNA 掺入增加(4-2 倍),G1 S移行加速;pRB的磷酸化形式的增多(3 倍).结论 cyclin E的高表达可明显影响MCF 7 细胞的生长、增殖,并可能通过pRB 磷酸化,影响细胞周期G1 S期移行而实现其对生长的调节。  相似文献   

8.
目的 分析DNA-PKcs、bcl-2、cyclin G在星形细胞瘤中的表达与肿瘤分化及预后的关系.方法 应用免疫组化S-P法对54例脑原发性星形细胞瘤中DNA-PKcs、bcl-2、cyclin G的表达进行检测,对其中41例取得随访资料的肿瘤患者存活因素进行分析.结果 DNA-PKcs、bcl-2表达在星形细胞瘤,间变型星形细胞瘤和多形性胶质母细胞瘤中有显著性差异.星形细胞瘤中DNA-PKcs、bcl-2、cyclin G表达率分别为90.74%,75.93%,62.96%.DNA-PKcs、bcl-2、cyclin G表达标记指数随着肿瘤恶性程度的增加而逐渐增高.三者标记指数高的肿瘤预后差.结论 DNA-PKcs、bcl-2、cyclin G过度表达与星形细胞瘤分化和预后密切相关,能够客观的反映肿瘤增生分化和恶性程度,可以作为判断星形细胞瘤分化和预后有价值的参考指标.  相似文献   

9.
A new human lymphoma cell line derived from pulmonary non-Hodgkin's lymphoma that developed in a renal transplant recipient was established from the patient's pleural effusion and designated PTLC-1. PTLC-1 grew aggressively in suspension, forming very loose clamps with a doubling time of about 18.9 h. The morphological, chromosomal, and immunophenotypic characteristics of the patient's tumor cells and PTLC-1 cells were very similar. PTLC-1 showed a monoclonal rearrangement of IgH gene and was highly tumorigenic in athymic nude mice. In situ hybridization, Southern blot hybridization and polymerase chain reaction demonstrated the presence of Epstein-Barr virus (EBV) genome in the patient's tumor and PTLC-1. PTLC-1 has been maintained in culture for over 60 months. Since EBV has been implicated in the pathogenesis of post-transplant lymphoma, this new cell line should serve as a useful experimental model for studying the etiology and biology of lymphoma developing in organ transplant recipients  相似文献   

10.
 目的探讨细胞周期蛋白Cyclin B1及细胞周期蛋白依赖性激酶CDK1在不同结直肠癌组织中的异常表 达及其临床意义。方法采用免疫组织化学法检测Cyclin B1、CDK1在11例正常结直肠组织、28例结直肠癌 组织和27例癌旁组织中的表达。结果Cyclin B1、CDK1在结直肠正常黏膜中表达阳性率为9.1%(1/11)和 18.2%(2/11),在结直肠癌组织中表达阳性率为89.3%(25/28)和92.9%(26/28),在癌旁组织中表达阳性率 为25.9%(7/27)和33.3%(9/27),各组之间相比差异有统计学意义(P<0.05)。不同分化程度结直肠癌之间 Cyclin B1、CDK1的阳性表达率差异无统计学意义(P>0.05)。结论Cyclin B1、CDK1在不同分化程度的结直 肠癌中均存在过表达现象,在癌旁组织中也有明显表达,可能在结直肠癌发生发展过程中起重要的调节作 用。  相似文献   

11.
We have examined whether and by what mechanism piceatannol inhibits cell cycle progression in DU145 cells. The treatment of cells with piceatannol for 24 h resulted in an increase in the percentage of cells in G1 phase and dose-dependent decreases in [3H]thymidine incorporation, as well as in protein levels of cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 and CDK4. Piceatannol exerted no effect on the levels of p21WAF1/CIP1 or p27KIP1. Piceatannol reduced CDK4 and CDK2 activity. These results indicate that delaying G1 cell cycle progression contributes to the piceatannol-mediated inhibition of DU145 cell growth, which may be mediated via the inhibition of CDK activity.  相似文献   

12.
目的:探讨Survivin、p53蛋白在鼻NK/T淋巴瘤中的表达及其与细胞凋亡和预后的关系。方法:应用TdT介导的dUTP缺口末端标记(TUNEL)技术和免疫组织化学链霉菌抗生物素蛋白-过氧化酶连接法(SP法),检测24例鼻NK/T淋巴瘤和17例良性淋巴结病变中细胞凋亡和Survivin、p53蛋白的表达水平。结果:Survivin、p53蛋白在鼻NK/T淋巴瘤表达的阳性率分别为45.8%(11/24)和62.5%(15/24);Survivin表达上调与p53高表达密切相关(P<0.05);凋亡指数与Survivin、p53蛋白明显呈负相关(P<0.005)。Survivin过表达者的平均生存时间明显短于阴性者(P=0.03),但p53表达和细胞凋亡指数与患者的预后无相关性(P>0.05)。结论:Survivin基因异常表达引起的凋亡抑制可能在鼻NK/T淋巴瘤的发生进展中有一定的作用,且与p53异常表达显著相关。Survivin表达可能是鼻NK/T淋巴瘤的一个新的预后不良因子。  相似文献   

13.
The protein p27Kp1 is one of the cyclin-dependent kinase inhibitors that are known to play important roles in the regulation of cell-cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin-dependent kinase inhibitors to histopathological grades of B-cell non-Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B-cell non-Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B-cell non-Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B-cell non-Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B-cell non-Hodgkin's lymphomas ( P <0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B-cell non-Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B-cell non-Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B-cell non-Hodgkin's lymphomas and in the prediction of prognosis.  相似文献   

14.
This study was undertaken to determine which if any presentment factors are statistically significant determinants of the clinical outcome in patients with non-Hodgkin's lymphoma. The pretreatment factors in 20 patients with T-cell lymphoma, including two patients with adult T-cell leukemia/ lymphoma (ATLL), and 28 patients with B-cell lymphoma were evaluated. In a stepwise logistic regression analysis, a T-cell phenotype in addition to high grade histology and pleural involvement demonstrated a statistically significant correlation with decreased response rate, when the analysis did not include patients with ATLL. Analysis by means of the Cox proportional hazards model disclosed that the T-cell phenotype retained a statistically significant correlation with survival after adjustments for other prognostic factors, whether the study included the patients with ATLL or not. The decreased response rate and survival of Japanese patients with non-Hodgkin's lymphoma in comparison with those reported in Western countries seem to be due to increased intrusion of T-cell lymphomas. To permit a reliable comparison of reports on new chemotherapeutic regimens from different institutions, the tumor phenotype must be determined in the population studied  相似文献   

15.
目的 探讨微小RNA-206(miR-206)对前列腺癌细胞中细胞周期蛋白依赖性激酶4(CDK4)和细胞周期素G相关蛋白激酶(GAK)表达的干扰作用及对前列腺癌细胞生长的影响.方法前列腺癌细胞株DU-145和PC-3为转染对象,转染miR-NC为对照组,转染miR-206为实验组.荧光实时定量PCR(qRT-PCR)检测CDK4和GAK mRNA的表达水平.Western blotting检测CDK4和GAK蛋白的表达水平.流式细胞术检测细胞周期分布.EdU增殖实验和集落形成实验检测细胞增殖能力.结果在DU-145和PC-3细胞株中,miR-NC组CDK4 mRNA表达量分别为1.00±0.09、1.00±0.10,GAK mRNA表达量为1.00±0.05、1.00±0.06;与之相比,两细胞株miR-206组中CDK4 mRNA表达明显下降,分别为0.36±0.18(t=6.572,P=0.001)、0.43±0.17(t=5.794,P=0.001),GAK mRNA表达量亦明显下降,分别为0.23±0.04(t=22.420,P<0.001)、0.32±0.08(t=14.500,P<0.001).Western blotting实验结果与qRT-PCR结果一致.流式细胞术检测结果显示,分别与两细胞株miR-NC组比较,转染miR-206后前列腺癌细胞在S期(23.60%±5.68%∶32.53%±4.52%,t=2.462,P=0.049;22.09%±4.35%∶30.96%±4.86%,t=2.720,P=0.035)和G2-M期(16.28%±7.12%∶26.63%±4.33%,t=2.484,P=0.048;14.60%±1.62%∶24.68%±7.13%,t=2.758,P=0.033)的细胞比例下降,在G0-G1期(60.13%±5.82%∶40.84%±5.37%,t=4.872,P=0.003;63.31%±3.27%∶44.36%±3.82%,t=7.533,P<0.001)的细胞比例升高.EdU增殖实验结果显示,转染miR-206的细胞增殖能力明显减弱(22.56±3.81∶38.90±8.51,t=3.503,P=0.013;25.12±6.42∶48.45±8.92,t=4.244,P=0.005).集落形成实验结果显示,两细胞株miR-NC组形成的集落数分别为218.66±44.59、177.35±24.49,miR-206组形成的集落数分别为125.38±32.80(t=3.370,P=0.015)、82.65±14.05(t=6.708,P=0.001),提示miR-206组细胞增殖能力降低.结论 miR-206可通过干扰CDK4和GAK的表达显著抑制前列腺癌细胞的生长,提示miR-206可能成为前列腺癌的分子靶向治疗工具.  相似文献   

16.
目的观察辛基酚对MCF-7乳腺癌细胞周期及周期蛋白表达的影响。方法以MTT试验、流式细胞分析、免疫细胞化学和RT-PCR等方法观察辛基酚对MCF-7乳腺癌细胞增殖、细胞周期相和细胞凋亡、CDK2和CDK4 mRNA表达、Cyclin D1 mRNA及蛋白表达的影响。结果4、8、16μmol/LOP作用MCF-7乳腺癌细胞72h时,细胞增殖率分别为107.31%、168.06%、62.00%,G0/G1期细胞分别为(52.46±6.67)%、(50.19±7.39)%、(67.31±5.47)%,对照组(55.27±7.53)%,细胞凋亡率分别为(4.84±1.12)%、(6.48±1.36)%、(19.26±3.57)%,对照组(5.56±1.125)%,16μmol/LOP减少了细胞中CDK2、CDK4、Cyclin D1 mRNA及Cyclin D1的表达。结论4、8μmol/LOP促进MCF-7乳腺癌细胞增殖,16μmol/LOP则抑制细胞增殖,促进细胞凋亡,这可能与OP影响细胞中CDK2、CDK4、Cyc-lin D1 mRNA及Cyclin D1表达有关。  相似文献   

17.
Background: Cervical cancer is one of the most prevalent gynecological cancers worldwide and contributes in highmortality of Indonesian women. The efficacy of chemotherapy as a standart therapy for cervical cancer decreases becauseit frequenly rises adverse effects. Recent studies have found that metformin has a potential anticancer effect mostlythrough reduction of cyclin expression and activation of Activated Adenosine Monophosphate Kinase (AMPK). Thisstudy aimed to investigate the effect of metfomin on expression of cyclin D1 and p53 and apoptosis in HeLa cancer cellline. Methods: HeLa cells were treated with various doses of metformin and doxorubicin as a positive control. Cytotoxiceffect of metformin was determined using the MTT assay. Immunocytochemistry was used to assess cyclin D1 and p53expression and apoptosis levels of treated HeLa cells were analyzed using flowcytometry. Data of cyclin D1 expressionwas statistically analyzed using the Kruskal-Wallis test followed by the Tamhane test, whilst ANOVA and Tukey postHoc tests were used to analyze data of p53 and apoptosis level. The significant value was p< 0.05. Results: Metforminwas able to inhibit proliferation of HeLa cells with IC50 60 mM. HeLa cells treated with 60 and 120 mM metforminhad lower cyclin D1 expression than HeLa cells treated without metformin and reached a significant difference (p=0.001). Moreover, 30 mM or higher doses of metformin increase significantly p53 expression (p< 0.001). Induction ofapoptosis was observed in HeLa cells treated with all doses of metformin and reached statistically difference (p= 0.04and p < 0.001). Conclusion: Metformin can modulate cyclin D1 and p53 expression in HeLa cancer cell line, leadingto inhibition of cell proliferation and induction of apoptosis. Other cyclin family members, CDK inhibitors and AMPKsignaling should be further investigated in order to know mechanism of metformin action.  相似文献   

18.
采用嗜银染技术对23例恶性淋巴瘤、8例淋巴结反应性增生和10例正常淋巴结的核仁组成区相关蛋白进行了显示(AgNOR)。结果显示恶性淋巴瘤的AgNOR核均数较高,与正常淋巴结和反应性淋巴结增生相比较有非常显著性差异(P<0.01)。不同恶性程度的非何杰金氏恶性淋巴瘤的AgNOR之间也有差异(P<0.05或P<0.01)。AgNOR方法有助于鉴别淋巴结的良恶性病变,在对恶性淋巴瘤的诊断和分型上有一定价值。  相似文献   

19.
目的:评价美罗华联合环磷酰胺、吡柔比星、长春新碱、泼尼松(R-CTOP 方案)治疗B 细胞非霍奇金淋巴瘤的疗效及不良反应,分析影响疗效的相关因素。方法:回顾性分析我院35例经病理证实为CD20+ 的B 细胞非霍奇金淋巴瘤患者的临床资料,评估R-CTOP 方案化疗的疗效及不良反应,分析性别、年龄、疾病分期、病理类型、LDH 水平及IPI 评分等影响疗效的相关因素。结果:35例患者中33例可评价疗效,其中完全缓解(CR)17例(51.5%),部分缓解(PR)11例(33.3%),有效率(CR+PR)84.8% 。23例初治患者中,CR13例(56.5%),PR8 例(34.8%),有效率(CR+ PR)91.3% ;10例复发难治患者中,CR4 例(40%),PR3 例(30%),有效率70% 。疗效与性别、疾病分期、病理类型、LDH 水平及IPI 评分等因素无显著相关,年龄对疗效有一定影响(P=0.012 )。 35例患者中无治疗相关死亡,不良反应主要为骨髓抑制(Ⅲ~Ⅳ度白细胞下降32.1%),心脏毒性和脱发较轻,主要为Ⅰ~Ⅱ级反应。其它不良反应经对症处理后均可耐受。结论:R-CTOP 方案治疗B 细胞非霍奇金淋巴瘤有效率高且不良反应轻微,可作为治疗B 细胞非霍奇金淋巴瘤特别是老年非霍奇金淋巴瘤患者的优先选择。   相似文献   

20.
目的:探讨Cyclin D1和CDK 4在新疆维吾尔族妇女宫颈癌发生、发展中的作用及相互关系.方法:采用免疫组化方法,检测100例宫颈癌组织和50例正常宫颈组织中Cyclin D1和CDK 4蛋白的表达情况.结果:宫颈癌组织中Cyclin D1 蛋白阳性表达率为75%,高于正常对照组的30%(P<0.01);CDK 4蛋白阳性表达率(87%),高于正常对照组(44%)(P<0.01).结论:Cyclin D1和CDK 4在新疆维吾尔族妇女宫颈癌中高表达,且与新疆维吾尔族妇女宫颈癌的发生、发展有关.  相似文献   

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