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1.
细胞周期蛋白cyclin B1与肿瘤 总被引:4,自引:0,他引:4
细胞周期蛋白cyclin B1与细胞周期蛋白依赖性蛋白激酶(cyclin-dependent protein kinases,CDKs)结合,受磷酸化、去磷酸化调节,所形成的活性复合物为MPF即细胞促分裂因子或M期促进因子,能转位入核,磷酸化其核内底物,促进细胞的G2/M期转变;并能通过磷酸化调节多种蛋白的活性与分布而参与纺锤体的形成和染色体的分离。cyclin B1在许多肿瘤中异常表达,呈现出癌基因的特性,cyclin B1过表达与定位的改变受p53、c-myc、H-Ras、Aurora A、Gadd45等多个基因的调节,而且与肿瘤发生发展、预后、诊断和治疗密切相关。 相似文献
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Moschovi M Alexiou GA Patereli A Stefanaki K Doussis-Anagnostopoulou I Stofas A Sfakianos G Prodromou N 《Journal of neuro-oncology》2011,103(3):699-704
Embryonal tumors constitute the most common malignant brain tumor group in children. Although patient prognosis has been substantially
improved over recent decades, identification of prognostic markers would be of obvious significance. In the present study
we evaluated the prognostic significance of cyclin A and B1 in correlation with Ki-67 index in pediatric embryonal tumors.
We retrospectively evaluated 53 children with embryonic tumors who were treated surgically in our institute. All patients
had regular follow-up examinations. The streptavidin–biotin–horseradish peroxidase (HRP) method was performed on paraffin
sections for detection of Ki-67/MIB-1, and cyclin A and B1. There were 42 cases of medulloblastoma (MB), 9 cases of atypical
teratoid/rhabdoid tumor (AT/RT), and 2 cases of supratentorial primitive neuroectodermal tumor (PNET). In MB patients, Ki-67
index >50% was associated with worse survival (P = 0.003). Cyclin A index >40% was associated with significantly poorer survival (P = 0.023). Patients with cyclin B1 index >15% exhibited a trend towards poorer survival (P = 0.068). On multivariate analysis, only Ki-67 index was identified as a factor with independent prognostic power. In AT/RT
and PNET, there was high expression of Ki-67 and variable expression of cyclin A and B1. Apart from Ki-67 index, cyclin A
may have a prognostic role. Study of the above indices at diagnosis could alter or intensify treatment methods, so as to improve
disease outcome. There is obviously a need for future studies with larger number of patients to confirm our preliminary observations. 相似文献
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Wu MH Chu CH Chou YC Chou WY Yang T Hsu GC Yu CP Yu JC Sun CA 《Breast cancer research and treatment》2011,129(3):777-784
The role of estrogen receptor beta (ERβ) in breast cancer is unclear. ERβ is considered to have a protective role in breast
cancer development based on findings demonstrating that ERβ expression inhibits ERα-mediated proliferation of breast cancer
cells. We previously demonstrated that ERβ causes a ligand independent G2 cell cycle arrest in MCF-7 cells. To study the mechanisms
of the ERβ-mediated G2 cell cycle arrest, we investigated its effects on the regulatory pathways responsible for the G2/M
phase transition. We found that ERβ inhibits CDK1 activity, which is the critical determinant of the G2/M progression. CDK1
activity is modulated by both stimulatory and inhibitory factors. Cyclin B1 is the major activator of CDK1. ERβ inhibited
the cell cycle-dependent stimulation of cyclin B1 mRNA and protein. GADD45A and BTG2 are two major inhibitors of CDK1, which
have been implicated in breast tumor formation. Based on these findings, we explored if the expression pattern of GADD45A
and BTG2 is affected by ERβ. We found that ERβ stimulates GADD45A and BTG2 mRNA levels. The induction of these two genes is
caused by ERβ binding directly to these genes and recruiting c-jun and NCOA2. Our findings demonstrated that unliganded ERβ
causes a G2 cell cycle arrest by inactivating CDK1 through the repression of cyclin B1 and stimulation of GADD45A and BTG2
expression. These results provide evidence that drugs that stimulate the production of unliganded ERβ may be effective new
therapies to prevent breast cancer. 相似文献
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Londero SC Godballe C Krogdahl A Bastholt L Specht L Sørensen CH Pedersen HB Pedersen U Christiansen P 《Acta oncologica (Stockholm, Sweden)》2008,47(3):451-457
Introduction. Papillary microcarcinomas (PMC) of the thyroid gland are defined according to The WHO Committee as papillary carcinomas measuring 10 mm or less in diameter. A large proportion of these tumours are found coincidentally in the treatment of symptomatic goitre and most cases follow an indolent course with an excellent prognosis. However, a more aggressive behaviour with regional and distant metastases does occur. The aim of this study was to evaluate if the immunohistochemical markers cyclin D1 or galectin-3 might indicate the presence of metastatic disease in patients with PMC at the time of diagnosis. Material and methods. From the 1st of January 1996 to 31st of December 2002 a total of 169 PMC patients were diagnosed and registered in the national Danish thyroid cancer database DATHYRCA and 131 of these were eligible for the study. Forty-three (33%) had histologically verified regional or distant metastases. Slides were cut from the primary tumour and immunostaining and quantification was subsequently performed. Results. The percentage of positive cells was examined for patients with and without metastases. For cyclin D1 the median values were 31% (range: 0-59) and 21% (range: 0-75), respectively, showing a statistically significant difference (p=0.02). For galectin-3 the medians were 87% (range: 6-96) and 85% (range: 0-99) and no significant difference was found. Conclusion. Cyclin D1 showed significantly higher median expression in patients with metastases compared to those without, indicating a correlation to tumour aggressiveness. However, both groups showed large variation in expression, which disqualify the marker as a discriminator for the detection of metastases. Galectin-3 was without any significant correlation to the presence of metastases from PMC. 相似文献
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Objective To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis
of breast cancer.
Methods High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in
the 60 cases of breast cancer tissues.
Results Abnormal immunoreactivities of α-and β-catenins were observed in 37 (61.7%) and 42 (70%) cases of breast cancer tissues, respectively.
There were 28 cases (46.7%) who showed cyclin D1 overexpression. The abnormal expression rates of α-and β-catenins in infiltrating
lobular carcinoma (ILC) were significantly higher than those in infiltrating ductal carcinoma (IDC) (P < 0.05), but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer (P > 0.05). The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer (P < 0.05), but not with histological type and the extent of differentiation (P > 0.05). Cyclin D1 overexpression was observed in 57.1% (24/42) of these cases that showed abnormal staining of β-catenin,
but only observed in 22.2% (4/18) of these cases with normal membranous staining of β-catenin. There was a significantly positive
correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 (r
s = 0.321, P < 0.05).
Conclusion The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression
in breast cancer. The abnormal expressions of α-and β-catenins are not a key factor in malignant cell metastasis in breast
cancer, but may also involve in the progress. 相似文献
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Esophageal squamous cell carcinoma (ESCC) is one of the most frequently diagnosed malignant tumors in North China. We have
identified that Wnt2/β-catenin pathway is activated in ESCC cells and sodium nitroprusside (SNP) and siRNA against β-catenin
not only inhibit the expressions of β-catenin and its major downstream effectors including c-myc and cyclin D1 but induce
cell cycle arrest and apoptosis. The purpose of the present study was to analyze the relationship between pathological parameters
including invasion depth and lymph node metastasis and the expressions of β-catenin, c-myc, and cyclin D1 in order to evaluate
their values of prognosis in patients with ESCC. The expressions of β-catenin, c-myc, and cyclin D1 were detected immunohistochemically
in the resected cancer tissues from 40 patients with ESCC. The β-catenin expression was reduced in 22 (55.0%) patients, which
was closely correlated with invasion depth (P = 0.023) and lymph node metastasis (P = 0.003). There was the positive c-myc expression in 21 (52.5%), which was significantly correlated with invasion depth (P = 0.009) and lymph node metastasis (P = 0.001). Furthermore, the results of survival rates analyzed by Kaplan–Meier curve revealed that patients with the reduced
expression of β-catenin had a poorer prognosis than those with the preserved expression (P = 0.031), and patients with the positive expression of c-myc also had a significantly poorer prognosis than those with the
negative expression (P = 0.008). These findings demonstrate that β-catenin pathway plays a crucial role in the progression of ESCC, suggesting that
both β-catenin and c-myc may be used as markers for predicting the prognosis of patients with ESCC. 相似文献
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目的 :探讨不同级别舌鳞癌组织中细胞周期相关蛋白cyclinA和cyclinD1基因转录情况。方法 :DIG标记及检测试剂盒进行组织原位杂交。结果 :舌鳞状细胞癌组织Ⅰ、Ⅱ、Ⅲ级中cyclinA基因转录阳性率分别为 47 6%、76 9%和 87 5 % ;cyclinD1基因转录阳性率分别为 62 0 %、 69 2 %和75 0 %。在有淋巴结转移的情况下 ,cyclinAmRNA和cyclinD1mRNA的表达较高。cy clinA和cyclinD1表达与舌鳞癌的恶性程度及淋巴结的转移均呈正相关 ,P <0 0 5。结论 :cyclinA和cyclinD1表达与舌鳞癌分化程度及淋巴结转移有关 ,可能是舌鳞癌预后不良的指标 相似文献
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人脑胶质瘤组织中cyclin D1和cyclin E表达的研究 总被引:1,自引:0,他引:1
目的:研究人脑胶质瘤中细胞周期素(cyclin) D1和cyclin E的表达与肿瘤病理等级的关系。方法:采用免疫组织化学法检测52例人脑胶质瘤和8例正常脑组织标本中cyclin D1和cyclin E的表达。结果:人脑胶质瘤组中有29例cyclin Dl的表达。随着胶质瘤病理分级增高,高、低恶性度胶质瘤的“阳”性率和平均标记指数均正著升高,两者差异有统计学意义,P<0.05。cyclin Dl与cyclin E的平均标记指数之同呈明显正相关,Pearson相关系数r-0.644,P<0.0l。结论:cyclin Dl与cyclin E在胶质瘤中被异常表达,是肿瘤发生和恶性转化的重要促进因子。 相似文献
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目的 :研究人脑胶质瘤中细胞周期素 (cyclin)D1和cyclinE的表达与肿瘤病理等级的关系。方法 :采用免疫组织化学法检测 5 2例人脑胶质瘤和 8例正常脑组织标本中cyclinD1和cyclinE的表达。结果 :人脑胶质瘤组中有 2 9例cyclinD1的表达。随着胶质瘤病理分级增高 ,高、低恶性度胶质瘤的阳性率和平均标记指数均显著升高 ,两者差异有统计学意义 ,P <0 0 5。cyclinD1与cyclinE的平均标记指数之间呈明显正相关 ,Pearson相关系数r =0 64 4,P <0 0 1。结论 :cyclinD1与cyclinE在胶质瘤中被异常表达 ,是肿瘤发生和恶性转化的重要促进因子。 相似文献
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Lv J Cao XF Ji L Zhu B Wang DD Tao L Li SQ 《Medical oncology (Northwood, London, England)》2012,29(1):151-160
In our previous study, Human Signal Transduction in Cancer Gene Array was used in 12 fresh tumor samples to detect the gene
expression profiles in the esophageal squamous cell carcinoma (ESCC) tissues matched adjacent non-cancerous samples. Among
genes up-regulated at least twofold, β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 were found. So subsequently, the aim of this
study was to investigate the prognosis and clinicopathologic roles of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC tissue.
The mRNA and protein expression levels of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 genes in 70 ESCC and adjacent non-cancerous
paraffin-embedded samples were determined by Real-Time Quantitative PCR (RT-PCR) and immunohistochemical staining. The mRNA
expression level of β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC was significantly higher than that in the adjacent non-cancerous
tissues (0.0821 ± 0.0416 vs. 0.0185 ± 0.0201, P = 0.0000; 1.9934 ± 1.9888 vs. 0.8863 ± 0.665, P = 0.0184; 0.0298 ± 0.0215 vs. 0.0189 ± 0.0187, P = 0.0017; 2.098 ± 0.091 vs. 1.016 ± 0.078, P = 0.0000; 2.181 ± 2.158 vs. 0.931 ± 0.894, P = 0.0152; respectively), and the protein expression level of determined genes was also significantly higher than that in
the adjacent non-cancerous tissues (0.2835 ± 0.0844 vs. 0.2352 ± 0.0670, P = 0.0003; 0.3830 ± 0.0947 vs. 0.2721 ± 0.1474, P = 0.0000; 0.2637 ± 0.0348 vs. 0.2042 ± 0.0180, P = 0.0000; 0.2058 ± 0.0316 vs. 0.1218 ± 0.0518, P = 0.0000; 0.2736 ± 0.0834 vs. 0.2251 ± 0.0571, P = 0.0001; respectively). Then, the overexpression of mRNA and protein levels of β-catenin, Wnt1 and Bmi-1 was aggressively
associated with lymph node metastasis, advanced pathological stage, and prognosis of the patients with ESCC (P < 0.05). The up-expression of Hoxa9 mRNA and protein was also aggressively associated with lymph node metastasis and advanced
pathological stage (P < 0.05); however, the overexpression of Hoxa9 protein was not associated with the prognosis (P > 0.05). Meanwhile, the hypo-expression of Smad4 mRNA was aggressively associated with advanced pathological stage and prognosis
of the patients with ESCC (P < 0.05); however, the hypo-expression of Smad4 protein was neutral to the prognosis and lymph node metastasis (P > 0.05). β-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 protein expression analysis showed that the positive outcomes of the combined
detection of Wnt1 and β-catenin expression or Wnt1, β-catenin and Bmi-1 expression were significantly worse than those of
a single target protein expression (P < 0.05). Meantime, the prognosis of the combined positive expression of Wnt1, β-catenin, and Bmi-1 was poorer than that in
the combined positive expression of Wnt1 and β-catenin (P < 0.05). The prognosis of ESCC patients with the overexpression of Wnt1/β-catenin and Bmi-1 was relatively poor, and the
level of Wnt1/β-catenin and Bmi-1 was conversely correlated with advanced pathological stage and lymph node metastasis. The
expression level of Smad4 and Hoxa9 mRNA was also associated with the prognosis of the patients with ESCC, pathological stage,
and lymph node metastasis; however, they might not be the independent prognostic factor. 相似文献
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Lakshmi Prabhu Rasika Mundade Benlian Wang Han Wei Antja-Voy Hartley Matthew Martin Kyle McElyea Constance J. Temm George Sandusky Yunlong Liu Tao Lu 《Oncotarget》2015,6(30):29396-29412
Y-box binding protein 1 [YBX1] is a multifunctional protein known to facilitate many of the hallmarks of cancer. Elevated levels of YBX1 protein are highly correlated with cancer progression, making it an excellent marker in cancer. The connection between YBX1 and the important nuclear factor κB [NF-κB] has never been reported. Here, we show that overexpression of wild type YBX1 [WT-YBX1] activates NF-κB, suggesting that YBX1 is a potential NF-κB activator. Furthermore, using mass spectrometry analysis we identified novel phosphorylation of serine 165 [S165] on YBX1. Overexpression of the S165A-YBX1 mutant in either HEK293 cells or colon cancer HT29 cells showed dramatically reduced NF-κB activating ability as compared with that of WT-YBX1, confirming that S165 phosphorylation is critical for the activation of NF-κB by YBX1. We also show that expression of the S165A-YBX1 mutant dramatically decreased the expression of NF-κB-inducible genes, reduced cell growth, and compromised tumorigenic ability as compared with WT-YBX1. Taken together, we provide the first evidence that YBX1 functions as a tumor promoter via NF-κB activation, and phosphorylation of S165 of YBX1 is critical for this function. Therefore, our important discovery may lead to blocking S165 phosphorylation as a potential therapeutic strategy to treat colon cancer. 相似文献
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目的探讨细胞周期素D1、E(cyclin D1、cyclin E)、p21cip1在pTNM Ⅰ期普通型肾细胞癌(CRCC)发生发展中的作用.方法用半定量RT-PCR方法,检测23例pTNM Ⅰ期CRCC组织和7例正常肾组织中cyclin D1、cyclin E及p21cip1的mRNA含量;用免疫组化方法检测CRCC中p53及ki-67的表达;并将以上指标与临床病理特征进行统计分析.结果 CRCC组织中cyclin D1、cyclin E、p21cip1mRNA含量分别为0.484±0.416、0.472±0.340、0.356±0.215,均高于正常对照组(0.078±0.051,P<0.01;0.063±0.063,P<0.01;0.178±0.114,P<0.05);Cyclin D1含量低者肿瘤直径小于3 cm(P<0.01);Cyclin E含量低者肿瘤常有坏死(P<0.05),细胞核分级较高(P<0.01);p21cip1低表达者细胞核分级较高(P<0.05);p21cip1与cyclin E呈正相关(γ=0.602,P<0.01).结论 pTNM Ⅰ期CRCC组织中cyclin D1、cyclin E、p21cip1mRNA含量升高,可能影响肿瘤的生物学行为及预后. 相似文献
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Zhiqiang Zhao Man-si Wu Changye Zou Qinglian Tang Jinchang Lu Dawei Liu Yuanzhong Wu Junqiang Yin Xianbiao Xie Jingnan Shen Tiebang Kang Jin Wang 《Cancer letters》2014
Monocarboxylate transporter isoform 1 (MCT1) is an important member of the proton-linked MCT family and has been reported in an array of human cancer cell lines and primary human tumors. MCT1 expression is associated with developing a new therapeutic approach for cancer. In this study, we initially showed that MCT1 is expressed in a variety of human osteosarcoma cell lines. Moreover, we evaluated the therapeutic response of targeting MCT1 using shRNA or MCT1 inhibitor. Inhibiting MCT1 delayed tumor growth in vitro and in vivo, including in an orthotopic model of osteosarcoma. Targeting MCT1 greatly enhanced the sensitivity of human osteosarcoma cells to the chemotherapeutic drugs adriamycin (ADM). In addition, we observed that MCT1 knockdown significantly suppressed the metastatic activity of osteosarcoma, including wound healing, invasion and migration. Further mechanistic studies revealed that the antitumor effects of targeting MCT1 might be related to the NF-κB pathway. Immunochemistry assay showed that MCT1 was an independent positive prognostic marker in osteosarcoma patients. In conclusion, our data, for the first time, demonstrate that MCT1 inhibition has antitumor potential which is associated with the NF-κB pathway, and high MCT1 expression predicates poor overall survival in patients with osteosarcoma. 相似文献