CDK1和CDC25B在卵巢上皮性癌组织中的表达及其意义
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摘要
背景和目的
卵巢恶性肿瘤是女性生殖器官三大恶性肿瘤之一,死亡率高居妇科恶性肿瘤之首。卵巢恶性肿瘤中以上皮性癌(Epithelial ovarian canceg EOC)最为多见,占原发卵巢恶性肿瘤的75%～90%。卵巢癌具有早期症状不明显,易转移,预后差等特点,已成为严重威胁妇女生命和健康的主要肿瘤。虽然CA_(125)是唯一确认辅助诊断的敏感指标,但其水平高低仅用于监测卵巢癌患者治疗中的病情缓解及恶化情况,目前仍缺乏相对较特异的生物学标记物可用于其早期诊断及预后判断,并且卵巢癌的发病机制还有待进一步研究。
肿瘤是一类以细胞生长和增殖失控为主要特征的疾病,细胞在增殖、分化和凋亡方面的异常都参与了肿瘤的发生和发展,其中细胞周期紊乱是肿瘤发生的最主要的机制。细胞周期蛋白依赖性激酶(Cyclin-dependent kinases,CDKs)是细胞周期调节的核心分子,与细胞周期蛋白(Cyclins)、细胞周期蛋白依赖性激酶抑制因子(Cyclin-dependent kinases inhibitors,CKIs)等共同组成细胞周期调控网络,调节细胞周期进程。细胞周期的整个调控网络中,各种分子的异常都有可能引起肿瘤的发生。CDK1是细胞周期G_2/M期的重要调节因子,在G_2晚期CDK1与细胞周期蛋白B1(CyclinB1)结合形成成熟促进因子(maturation promoting factor,MPF),CDK1分子构象发生改变,暴露14位苏氨酸和15位酪氨酸(Thr14/TVr15)残基,CDC25B通过去磷酸化CDK1的Thr14/Tyr15激活MPF,促进细胞由G_2期进入M期,加速细胞分裂,对细胞周期进程起正调控作用。
本研究应用免疫组化SP法,检测20例正常卵巢组织、20例卵巢良性上皮性肿瘤组织及76例卵巢上皮性癌组织中CDK1和CDC25B蛋白的表达情况,并分析CDK1和CDC25B蛋白表达与卵巢上皮性癌各种临床病理因素的关系,探讨CDK1和CDC25B在卵巢上皮性癌发生、发展中的作用。
材料和方法
1.收集郑州大学第一附属医院病理科2004年11月至2007年9月妇科手术存档蜡块116例,其中正常卵巢组织20例,卵巢良性上皮性肿瘤组织20例(浆液性10例,黏液性10例),卵巢上皮性癌组织76例(浆液性54例,黏液性22例)。卵巢上皮性癌按FIGO标准分期:Ⅰ期10例,Ⅱ期14例,Ⅲ期48例,Ⅳ期4例;组织学分级:G_114例,G_222例,G_340例;淋巴结转移24例,无淋巴结转移52例。所有标本临床病理资料完整,诊断均经病理科医师核实,患者年龄19岁～82岁,平均年龄51.9±13.5岁。所有卵巢上皮性癌患者均为原发,术前未接受过放疗或化疗。
2.采用免疫组化SP法检测76例卵巢上皮性癌组织、20例卵巢良性上皮性肿瘤组织和20例正常卵巢组织中CDK1和CDC25B蛋白的表达情况,分析CDK1和CDC25B蛋白表达与卵巢上皮性癌临床病理因素之间的关系。
3.统计学分析:应用SPSS13.0软件包进行统计学分析,计数资料采用χ~2检验和相关性分析,以双侧α=0.05作为检验水准。
结果
1.CDK1主要在胞浆中表达,在正常卵巢组织、卵巢良性上皮性肿瘤组织和卵巢上皮性癌组织中的阳性表达率分别为15.0%、30.0%和86.8%;卵巢上皮性癌组织中的阳性表达率显著高于正常卵巢组织和卵巢良性上皮性肿瘤组织(P＜0.05),卵巢良性上皮性肿瘤组织与正常卵巢组织相比,表达差异无统计学意义(P=0.256)。
2.CDK1的表达与卵巢上皮性癌临床病理特征的关系:CDK1的表达与卵巢上皮性癌的分化程度、组织学类型、临床分期、患病年龄及有无淋巴结转移均无明显相关性(P＞0.05)。
3.CDC25B主要在胞核中表达,在正常卵巢组织、卵巢良性上皮性肿瘤组织和卵巢上皮性癌组织中的阳性表达率分别为0.0%、20.0%、57.9%;卵巢上皮性癌组织中的阳性表达率显著高于正常卵巢组织和卵巢良性上皮性肿瘤组织(P＜0.05),卵巢良性上皮性肿瘤组织与正常卵巢组织相比,表达差异无统计学意义(P=0.035,行χ~2分割,α=0.05/3=0.0167)。
4.CDC25B的表达与卵巢上皮性癌临床病理特征的关系:CDC25B的表达与卵巢上皮性癌的临床分期及有无淋巴结转移明显相关(P＜0.05);临床分期Ⅲ、Ⅳ期与Ⅰ、Ⅱ期相比,阳性表达率显著增高(P＜0.05),Ⅰ期与Ⅱ期相比,表达差异无统计学意义(P=1.000);淋巴结转移组CDC25B阳性表达率显著高于无淋巴结转移组,差异有统计学意义(P＜0.05)。CDC25B的表达与卵巢上皮性癌分化程度、组织学类型和患病年龄均无关(P＞0.05)。
5.CDK1和CDC25B在卵巢上皮性癌组织中表达的相关性:在76例卵巢上皮性癌组织中,CDK1与CDC25B表达结果一致者52例(68.4%),二者共阳性43例,共阴性9例;CDK1阳性表达组中CDC25B的阳性表达率为65.2%(43/66),显著高于阴性组10.0%(1/10)。二者相关系数为0.378,呈正相关(P＜0.05)。
结论
1.CDK1过表达可能促进卵巢癌的恶性增殖,参与卵巢癌的发生发展;
2.CDC25B过表达可能与卵巢癌的发生、发展及其浸润、转移有关;
3.CDK1和CDC25B在卵巢癌的发生中可能具有协同作用。
Background
Malignant ovarian tumors are one of the three kinds of malignant tumors of female genital system,and it is the leading cause of death from gynecologic malignancies.Epithelial ovarian cancer(EOC) is the most common,accounting for 75%～90%of the primary ovarian malignancy.Because of lack of early warning signs and typical symptomatology,metastatic easily and poor prognosis,EOC has become a serious threaten to the lives and health of women.Although CA_(125) is the only confirmed sensitive diagnosis indicator,but it is only applied to monitor the level of relif or deterioration of the patients' condition.Furthermore the relatively specific biomarker used for early diagnosis and prognosis judgement is still not found,so researching the new effective indicator for which,improving the survival rate of patients with ovarian carcinoma,is the most considerable subject of all.
Cell growth and proliferation being out of the control is the main characteristic of the malignancy.The abnormal of cell proliferation,differentiation and apoptosis are involved in the tumorigenesis and development,and the disorder of cell cycle regulation mechanism plays an important role in carcinogenesis.Cyclin-dependent kinases(CDKs) are the core molecule of cell cycle regulation mechanism,which with Cyclins,CDKs inhibitor(CKIs) and so on compose the network of cell cycle regulation,contributing cell cycle progression.CDKI plays an important role in G_2/M phase,at the late G_2 phase CDK1 combines with CyclinB1 to form maturation promoting factor(MPF),causing CDK1 molecular conformation changed and exposing Thr14/Tyr15 residues.CDC25B phosphatase dephosphorylate Thr14/Tyr15 residues to activates MPF,promotes the cell cycle progression and cell division.
Objective
In this study,Streptavidin-Peroxidase(SP) immunohistochemistry technique was used to detecte the expressions of CDK1 and CDC25B protein in 20 cases normal ovarian tissues,20 cases benign epithelial ovarian tumor tissues and 76 cases epithelial ovarian cancer tissues,then analyze the correlations and relations of their expressions and the clinicopathological features,to identify the roles of CDK1 and CDC25B in the tumorigenesis and development of EOC.
Materials and methods
1.Collect paraffin imbedding ovarian tissues of 20 hysteromyoma patients and 96 ovarian epithelial tumors,who had pathological and clinical integrity data and underwent gynecological operation at the Department of Gynecology,the First Affiliated Hospital of Zhengzhou University,from November 2004 to September 2007.All the patients didn t get any radiotherapy,chemotherapy and other therapy before operation.Among them,there are 76 epithelial ovarian cancers(include 54 serous cystadenocarcinoma,22 mucinous cystadenocarcinoma),20 ovarian benign ovarian epithelial tumors(10 serous cystadenoma,10 mucinous cystadenoma).
2.Streptavidin-Peroxidase(SP) immunohistochemistry technique was used to detecte the expression of CDK1 and CDC25B protein in 76 cases of epithelial ovarian cancer,20 cases of ovarian benign epithelial tumor and 20 cases of normal ovarian tissues,analyze the correlations and relations between their expressions and the clinicopathological features of EOC.
3.Statistical analysis:the SPSS statistical package program 13.0 was performed for all analysis.Association of CDK1 and CDC25B expressions in different ovarian tissues were tested by Chi-square Test,the correlation of CDK1 and CDC25B expressions in the epithelial ovarian cancer were tested by Spearman Correlation test. There was a statistical significance when P＜0.05.
Results
1.CDK1 is mainly localizated in the cytoplasm,the positive rate of CDK1 protein expression in normal ovary,benign ovarian epithelial tumor and epithelial ovarian cancer were 15.0%(3/20),30.0%(6/20)and 86.8%(66/76) respectively;The expression in EOC is significantly higher than that in normal ovary and benign ovarian epithelial tumor(P＜0.05),there is no statistical difference between normal ovary and benign ovarian epithelial tumor(P=0.256).
2.The expression of CDK1 protein in EOC wasn't significantly associated with the histological grade,pathological subtype,FIGO stage,age and lymph node metastases(P＞0.05).
3.CDC25B is mainly localizated in the nucleus,the positive rate of CDC25B protein expression in normal ovary,benign ovarian epithelial tumor and epithelial ovarian cancer were 0.0%(0/20),20.0%(4/20)and 57.9%(44/76) respectively;The expression in EOC is significantly higher than that in normal ovary and benign ovarian epithelial tumor(P＜0.05),there is no statistical difference between normal ovary and benign ovarian epithelial tumor(P=0.035).
4.The expression of CDC25B protein in EOC was significantly associated with the FIGO stage and lymph node metastasis(P＜0.05),and wasn't significantly associated with the histological grade,pathological subtype and age(P＞0.05).The positive rate of CDC25B protein expression in tissues with FIGOⅢ,Ⅳstage was significantly higher than that ofⅠ、Ⅱstage(P＜0.05),there is no statistical difference between FIGOⅠandⅡstage(P=1.000).The positive rate of CDC25B protein expression in tissues with lymphoid node metastasis was significantly higher than that of without lymphoid node metastasis(P＜0.05).
5.The correlation between the expression of CDK1 and CDC25B protein in EOC:The positive rate of CDK1 and CDC25B protein co-expression is 56.6% (43/76),the correlation coefficient was 0.378.There was positive correlation between the expression of CDK1 and CDC25B protein in EOC(P＜0.05).
Conclusions
1.The overexpression of CDK1 protein may contribute to the malignant proliferation of tumor and play an important role in carcinogenesis and progression of epithelial ovarian cancer.
2.The overexpression of CDC25B protein may be associated with the carcinogenesis,progression,invasion and metastasis of epithelial ovarian cancer.
3.The overexpression of CDK1 and CDC25B protein may have synergistic effect in the carcinogenesis of epithelial ovarian cancer.
卵巢恶性肿瘤是女性生殖器官三大恶性肿瘤之一,死亡率高居妇科恶性肿瘤之首。卵巢恶性肿瘤中以上皮性癌(Epithelial ovarian canceg EOC)最为多见,占原发卵巢恶性肿瘤的75%～90%。卵巢癌具有早期症状不明显,易转移,预后差等特点,已成为严重威胁妇女生命和健康的主要肿瘤。虽然CA_(125)是唯一确认辅助诊断的敏感指标,但其水平高低仅用于监测卵巢癌患者治疗中的病情缓解及恶化情况,目前仍缺乏相对较特异的生物学标记物可用于其早期诊断及预后判断,并且卵巢癌的发病机制还有待进一步研究。
肿瘤是一类以细胞生长和增殖失控为主要特征的疾病,细胞在增殖、分化和凋亡方面的异常都参与了肿瘤的发生和发展,其中细胞周期紊乱是肿瘤发生的最主要的机制。细胞周期蛋白依赖性激酶(Cyclin-dependent kinases,CDKs)是细胞周期调节的核心分子,与细胞周期蛋白(Cyclins)、细胞周期蛋白依赖性激酶抑制因子(Cyclin-dependent kinases inhibitors,CKIs)等共同组成细胞周期调控网络,调节细胞周期进程。细胞周期的整个调控网络中,各种分子的异常都有可能引起肿瘤的发生。CDK1是细胞周期G_2/M期的重要调节因子,在G_2晚期CDK1与细胞周期蛋白B1(CyclinB1)结合形成成熟促进因子(maturation promoting factor,MPF),CDK1分子构象发生改变,暴露14位苏氨酸和15位酪氨酸(Thr14/TVr15)残基,CDC25B通过去磷酸化CDK1的Thr14/Tyr15激活MPF,促进细胞由G_2期进入M期,加速细胞分裂,对细胞周期进程起正调控作用。
本研究应用免疫组化SP法,检测20例正常卵巢组织、20例卵巢良性上皮性肿瘤组织及76例卵巢上皮性癌组织中CDK1和CDC25B蛋白的表达情况,并分析CDK1和CDC25B蛋白表达与卵巢上皮性癌各种临床病理因素的关系,探讨CDK1和CDC25B在卵巢上皮性癌发生、发展中的作用。
材料和方法
1.收集郑州大学第一附属医院病理科2004年11月至2007年9月妇科手术存档蜡块116例,其中正常卵巢组织20例,卵巢良性上皮性肿瘤组织20例(浆液性10例,黏液性10例),卵巢上皮性癌组织76例(浆液性54例,黏液性22例)。卵巢上皮性癌按FIGO标准分期:Ⅰ期10例,Ⅱ期14例,Ⅲ期48例,Ⅳ期4例;组织学分级:G_114例,G_222例,G_340例;淋巴结转移24例,无淋巴结转移52例。所有标本临床病理资料完整,诊断均经病理科医师核实,患者年龄19岁～82岁,平均年龄51.9±13.5岁。所有卵巢上皮性癌患者均为原发,术前未接受过放疗或化疗。
2.采用免疫组化SP法检测76例卵巢上皮性癌组织、20例卵巢良性上皮性肿瘤组织和20例正常卵巢组织中CDK1和CDC25B蛋白的表达情况,分析CDK1和CDC25B蛋白表达与卵巢上皮性癌临床病理因素之间的关系。
3.统计学分析:应用SPSS13.0软件包进行统计学分析,计数资料采用χ~2检验和相关性分析,以双侧α=0.05作为检验水准。
结果
1.CDK1主要在胞浆中表达,在正常卵巢组织、卵巢良性上皮性肿瘤组织和卵巢上皮性癌组织中的阳性表达率分别为15.0%、30.0%和86.8%;卵巢上皮性癌组织中的阳性表达率显著高于正常卵巢组织和卵巢良性上皮性肿瘤组织(P＜0.05),卵巢良性上皮性肿瘤组织与正常卵巢组织相比,表达差异无统计学意义(P=0.256)。
2.CDK1的表达与卵巢上皮性癌临床病理特征的关系:CDK1的表达与卵巢上皮性癌的分化程度、组织学类型、临床分期、患病年龄及有无淋巴结转移均无明显相关性(P＞0.05)。
3.CDC25B主要在胞核中表达,在正常卵巢组织、卵巢良性上皮性肿瘤组织和卵巢上皮性癌组织中的阳性表达率分别为0.0%、20.0%、57.9%;卵巢上皮性癌组织中的阳性表达率显著高于正常卵巢组织和卵巢良性上皮性肿瘤组织(P＜0.05),卵巢良性上皮性肿瘤组织与正常卵巢组织相比,表达差异无统计学意义(P=0.035,行χ~2分割,α=0.05/3=0.0167)。
4.CDC25B的表达与卵巢上皮性癌临床病理特征的关系:CDC25B的表达与卵巢上皮性癌的临床分期及有无淋巴结转移明显相关(P＜0.05);临床分期Ⅲ、Ⅳ期与Ⅰ、Ⅱ期相比,阳性表达率显著增高(P＜0.05),Ⅰ期与Ⅱ期相比,表达差异无统计学意义(P=1.000);淋巴结转移组CDC25B阳性表达率显著高于无淋巴结转移组,差异有统计学意义(P＜0.05)。CDC25B的表达与卵巢上皮性癌分化程度、组织学类型和患病年龄均无关(P＞0.05)。
5.CDK1和CDC25B在卵巢上皮性癌组织中表达的相关性:在76例卵巢上皮性癌组织中,CDK1与CDC25B表达结果一致者52例(68.4%),二者共阳性43例,共阴性9例;CDK1阳性表达组中CDC25B的阳性表达率为65.2%(43/66),显著高于阴性组10.0%(1/10)。二者相关系数为0.378,呈正相关(P＜0.05)。
结论
1.CDK1过表达可能促进卵巢癌的恶性增殖,参与卵巢癌的发生发展;
2.CDC25B过表达可能与卵巢癌的发生、发展及其浸润、转移有关;
3.CDK1和CDC25B在卵巢癌的发生中可能具有协同作用。
Background
Malignant ovarian tumors are one of the three kinds of malignant tumors of female genital system,and it is the leading cause of death from gynecologic malignancies.Epithelial ovarian cancer(EOC) is the most common,accounting for 75%～90%of the primary ovarian malignancy.Because of lack of early warning signs and typical symptomatology,metastatic easily and poor prognosis,EOC has become a serious threaten to the lives and health of women.Although CA_(125) is the only confirmed sensitive diagnosis indicator,but it is only applied to monitor the level of relif or deterioration of the patients' condition.Furthermore the relatively specific biomarker used for early diagnosis and prognosis judgement is still not found,so researching the new effective indicator for which,improving the survival rate of patients with ovarian carcinoma,is the most considerable subject of all.
Cell growth and proliferation being out of the control is the main characteristic of the malignancy.The abnormal of cell proliferation,differentiation and apoptosis are involved in the tumorigenesis and development,and the disorder of cell cycle regulation mechanism plays an important role in carcinogenesis.Cyclin-dependent kinases(CDKs) are the core molecule of cell cycle regulation mechanism,which with Cyclins,CDKs inhibitor(CKIs) and so on compose the network of cell cycle regulation,contributing cell cycle progression.CDKI plays an important role in G_2/M phase,at the late G_2 phase CDK1 combines with CyclinB1 to form maturation promoting factor(MPF),causing CDK1 molecular conformation changed and exposing Thr14/Tyr15 residues.CDC25B phosphatase dephosphorylate Thr14/Tyr15 residues to activates MPF,promotes the cell cycle progression and cell division.
Objective
In this study,Streptavidin-Peroxidase(SP) immunohistochemistry technique was used to detecte the expressions of CDK1 and CDC25B protein in 20 cases normal ovarian tissues,20 cases benign epithelial ovarian tumor tissues and 76 cases epithelial ovarian cancer tissues,then analyze the correlations and relations of their expressions and the clinicopathological features,to identify the roles of CDK1 and CDC25B in the tumorigenesis and development of EOC.
Materials and methods
1.Collect paraffin imbedding ovarian tissues of 20 hysteromyoma patients and 96 ovarian epithelial tumors,who had pathological and clinical integrity data and underwent gynecological operation at the Department of Gynecology,the First Affiliated Hospital of Zhengzhou University,from November 2004 to September 2007.All the patients didn t get any radiotherapy,chemotherapy and other therapy before operation.Among them,there are 76 epithelial ovarian cancers(include 54 serous cystadenocarcinoma,22 mucinous cystadenocarcinoma),20 ovarian benign ovarian epithelial tumors(10 serous cystadenoma,10 mucinous cystadenoma).
2.Streptavidin-Peroxidase(SP) immunohistochemistry technique was used to detecte the expression of CDK1 and CDC25B protein in 76 cases of epithelial ovarian cancer,20 cases of ovarian benign epithelial tumor and 20 cases of normal ovarian tissues,analyze the correlations and relations between their expressions and the clinicopathological features of EOC.
3.Statistical analysis:the SPSS statistical package program 13.0 was performed for all analysis.Association of CDK1 and CDC25B expressions in different ovarian tissues were tested by Chi-square Test,the correlation of CDK1 and CDC25B expressions in the epithelial ovarian cancer were tested by Spearman Correlation test. There was a statistical significance when P＜0.05.
Results
1.CDK1 is mainly localizated in the cytoplasm,the positive rate of CDK1 protein expression in normal ovary,benign ovarian epithelial tumor and epithelial ovarian cancer were 15.0%(3/20),30.0%(6/20)and 86.8%(66/76) respectively;The expression in EOC is significantly higher than that in normal ovary and benign ovarian epithelial tumor(P＜0.05),there is no statistical difference between normal ovary and benign ovarian epithelial tumor(P=0.256).
2.The expression of CDK1 protein in EOC wasn't significantly associated with the histological grade,pathological subtype,FIGO stage,age and lymph node metastases(P＞0.05).
3.CDC25B is mainly localizated in the nucleus,the positive rate of CDC25B protein expression in normal ovary,benign ovarian epithelial tumor and epithelial ovarian cancer were 0.0%(0/20),20.0%(4/20)and 57.9%(44/76) respectively;The expression in EOC is significantly higher than that in normal ovary and benign ovarian epithelial tumor(P＜0.05),there is no statistical difference between normal ovary and benign ovarian epithelial tumor(P=0.035).
4.The expression of CDC25B protein in EOC was significantly associated with the FIGO stage and lymph node metastasis(P＜0.05),and wasn't significantly associated with the histological grade,pathological subtype and age(P＞0.05).The positive rate of CDC25B protein expression in tissues with FIGOⅢ,Ⅳstage was significantly higher than that ofⅠ、Ⅱstage(P＜0.05),there is no statistical difference between FIGOⅠandⅡstage(P=1.000).The positive rate of CDC25B protein expression in tissues with lymphoid node metastasis was significantly higher than that of without lymphoid node metastasis(P＜0.05).
5.The correlation between the expression of CDK1 and CDC25B protein in EOC:The positive rate of CDK1 and CDC25B protein co-expression is 56.6% (43/76),the correlation coefficient was 0.378.There was positive correlation between the expression of CDK1 and CDC25B protein in EOC(P＜0.05).
Conclusions
1.The overexpression of CDK1 protein may contribute to the malignant proliferation of tumor and play an important role in carcinogenesis and progression of epithelial ovarian cancer.
2.The overexpression of CDC25B protein may be associated with the carcinogenesis,progression,invasion and metastasis of epithelial ovarian cancer.
3.The overexpression of CDK1 and CDC25B protein may have synergistic effect in the carcinogenesis of epithelial ovarian cancer.
引文
1.曹泽毅.中华妇产科学,2004,2:2163.
2.Lindqvist A,Kallstrom H,Lundgren A,et al.CDC25B cooperates with CDC25A to induce mitosis but has a unique role in activating Cyclin B12CDK1at the centrosome[J].J Cell Biol,2005,171(1):35-45.
3.乐杰.妇产科学,2008,7:279.
4.Lolli G,Johnson LN.CAK-Cyclin-dependent Activating Kinase:a key kinase in cell cycle control and a target for drugs?[J].Cell Cycle,2005,4(4):572-577.
5.Lolli G,Johnson LN.Recognition of CDK2 by CDK7.Proteins,2007,67(4):1048-1059.
6.Forester CM,Maddox J,Louis JV,et al.Control of mitotic exit by PP2A regula tion of Cdc25C and CDK1.Proc Natl Acad Sci U S A.2007 Dec 11;104(50):19867-19872.
7.Stark GR,Taylor WR.Control of the G_2/M transition.Mol Biotechenol,2006,32:227-248.
8.De Souza CP,Ellem KA,Gabrielli BG.Centrosomal and cytoplasmic Cdc2/CyclinB1 activation precedes nuclear mitotic events[J].Exp Cell Res,2000,257(1):11-21.
9.Bonnet J,Coopman P,Morris MC.Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis.Cell Cycle,2008,7(13):1991-1998.
10.Lindqvist A,van Zon W,Karlsson Rosenthal C,et al.CyclinB1-CDK1 activation continues after centrosome separation to control mitotic progression.PLoS Biol,2007,5(5):123.
11.Nigg EA.Mitotic kinases as regulators of cell division and its checkpoints[J].Nat Rev Mol Cell Biol,2001,2(1):21-32.
12.Wong OK,Fang G.CDK1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1 mediated formation of the 3F3/2 epitope.J Cell Biol,2007,179(4):611-617.
13. Orchard C B , Siciliano I, Sorrell D A , et al. Tobacco BY-2 cells expressing fission yeast CDC25 bypass a G_2/ M block on the cell cycle[J]. The Plant Journal,2005 ,442:290-299.
14. L(?)ffler H, Rebacz B, Ho AD, et al. Chk1-dependent regulation of CDC25B functions to coordinate mitotic events. Cell Cycle, 2006,1 ;5(21 ):2543-2547.
15. Boutros R, Ducommun B. Asymmetric localization of the CDC25B phosphatase to the mother centrosome during interphase. Cell Cycle,2008 Febl;7(3):401-406.
16. Dutertre S, Cazales M , Quaranta M , et al. Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G_2 -M transition[J].J Cell Sci ,2004,117(12):2523-2531.
17. Lobjois V, Jullien D, Bouch(?) JP, et al. The polo-like kinase 1 regulates CDC25B -dependent mitosis entry. Biochim Biophys Acta, 2009,1793(3):462-468.
18. Baldin V, Pelel K, Cazales M, et al. Nuclear localization of CDC25B1 and serine 146 integrity are required for induction of mitosis[J],J Biol Chem, 2002, 277(38):35176-35182.
19. Bansal P, Lazo JS. Induction of CDC25B regulates cell cycle resumption after genotoxic stress. Cancer Res, 2007,67(7):3356-3363.
20. Aressy B, Ducommun B. Cell cycle control by the CDC25 phosphatases. Anticancer Agents Med Chem, 2008 ,8(8):818-824.
21. Kramer A , Mailand N , Lukas C, et al. Centrosome-associated Chkl prevents premature activation of Cyclin2B2CDKl kinase[J ].Nat,Cell Biol,2004,6(9):884-891.
22. Santamaria D, Barri(?)re C, Cerqueira A,et al. CDKl is sufficient to drive the mammalian cell cycle. Nature, 2007 ,448(7155):811-815.
23. Willim K, Richard SP. DNA damaged and cell cycle checkpoint s.The FASEB [J],1996,10:238.
24. Khandan K,Arthur BP. Redundant Cyclin over expression and gene amplication in breast cancer cells. Pro Natl Acad Sci USA,1993,90:1112.
25. Juliano R.Movin' on through with Cdc2. Nat Cell Biol ,2003,5:589-590.
26. Liu P, Kao TP, Huang H. CDK1 promotes cell proliferation and survival via phosphorylation and inhibition of FOXO1 transcription factor. Oncogene,2008,27 (34):4733-4744.
27. Senju M ,Sueoka N,Satato A,et al. Hsp90 inhibitors cause G_2/M arrest associated with the reductionof Cdc25C and Cdc2 in lung cancer cell lines[J ]. J Cancer Res Clin Oncol ,2006,132 (3): 150-158.
28. Banerjee SK,Weston AP,Zoubine MN ,et al. Expression of cdc2 and CyclinBl in helicobacter pylori associated gastric MALT and MALT lymphoma: relationship to cell death , proliferation ,and transformation [J]. Am J Pathol ,2000,156(1):217-225.
29. Sarela AI,Verbeke CS,Ramsdale J ,et al. Expression of survivin ,a novel inhibitor of apoptosis and cell cycle regulatory protein ,in pancreatic adenocarcinoma [J].Br J Cancer ,2002 ,86(6):886-892.
30. Welsh JB, Zarrinkar PP, Sapinoso LM, et al. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer [J]. Proc Natl Acad Sci USA, 2001,98(3):1176-1181.
31. Chen H, Huang Q, Zhai DZ,et al.CDK1 expression and effects of CDK1 silencing on the malignant phenotype of glioma cells.Zhonghua Zhong Liu Za Zhi, 2007,29 (7):484-488.
32. Kourea HP, Koutras AK, Scopa CD, et al. Expression of the cell cycle regulatory protein p34cdc2, p21waf1, and p53 in node negative invasive ductal breast carcino ma.M ol Pathol, 2003,56:328-335.
33. Kim SJ, Nakayama S, Miyoshi Y, et,al. Determination of the specific activity of CDK1 and CDK2 as a novel prognostic indicator for early breast cancer. Ann Oncol, 2008,19:68-72.
34. NozoeT, Honda M , Inutsuka S, etal. P34cdc2 expression is an independent indicator for lymph node metastasis in colorectal carcinoma.Cancer Res Clin Oricof, 2003,129:498-502.
35. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm.Nat Rev Cancer, 2009,9(3): 153-166.
36. Warenius HM, Seabra L, Kyritsi L, et al. Theranostic proteomic profiling of Cyclins, Cyclin dependent kinases and Ras in human cancer cell lines is dependent on p53 mutational status. Int J Oncol, 2008,32(4):895-907.
37. Nakayama S, Torikoshi Y, Takahashi T, et al. Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells. Breast Cancer Res,2009,11(1):12.
38. Beatrix B, Muriel Q, Bernadette A.Genotoxic-activated G_2-M checkpoint exit is dependent on CDC25B phosphatase expression. Mol Cancer Ther, 2006,5:1446-1451.
39. Srivastava SK, Bansal P, Oguri T,et,al.Cell division cycle 25B phosphatase is essential for benzo(a)pyrene-7,8-Diol-9,10-epoxide induced neoplastic transfor mation. Cancer Res, 2007, 67: 9150-9157 .
40. Boutros R, Lobjois V, Ducommun B. CDC25B involvement in the centrosome duplication cycle and in microtubule nucleation. Cancer Res, 2007,67:11557-11564.
41. Lazo J S, Nemoto K, Pestell K E, et al. Identification of a potent and selective pharmacophore for CDC25 dual specificity phosphatase inhibitors[J]. Mol Pharmacol, 2002, 61(4):720-728.
42. Lazo J S, Asian D C, Southwick E C, et al. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase CDC25[J ]. J Med Chem, 2001,44(24):4042-4049.
43. Sodeoka M , Sampe R , Kojima S, et al. Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR andCDC25B inhibition[J]. Med Chem, 2001, 44(20):3216-3222.
44. Varmeh S, Manfredi JJ. Inappropriate activation of Cyclin-dependent kinases by the phosphatase CDC25B results in premature mitotic entry and triggers a p53-dependent checkpoint. J Biol Chem, 2009,45(2):32-36.
45. Broggini M, Buraggi G, Brenna A, et al. Cell cycle related phosphatases CDC25A and B expression correlates with survival in ovarian cancer patients [J].Anticancer Res,2000,20 (60):4835-4840.
46. Takemasa I,Yamamoto H,Sekimoto M,et al. Overexpression of CDC25B phosphatase as a novel marker of poor prognosis of human colorectal carcinoma [J].CancerRes,2000,60(11):3043-3050.
47. Boldrini L, Gisfredi S, Ursino S, et al. CDC25B: relationship with angiogenesis and prognosis in non-small cell lung carcinoma. Hum Pathol, 2007,38(10): 1563-1568.
48. Aressy B, Bugler B, Valette A, et al. Moderate variations in CDC25B protein levels modulate the response to DNA damaging agents. Cell Cycle, 2008,7(14):2234-2240.
49. Chen RQ, Yang QK, Lu BW, et al. CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res, 2009,69(6):2663-2668.
50. Varmeh-Ziaie S, Manfredi JJ. The dual specificity phosphatase CDC25B, but not the closely related Cdc25C, is capable of inhibiting cellular proliferation in a manner dependent upon its catalytic activity. J Biol Chem,2007,282(34):24633-24641.
51. Galaktinov K, Lee AK, Eckstein J, et al. cdc25 cell-cycle phosphatase as potential human oncogenesis. Science ,1995,269:1575-1577.
52. Boutros R, Lobjois V, Ducommun B. CDC25B involvement in the centrosome duplication cycle and in microtubule nucleation. Cancer Res,2007,67(24):11557-11564.
1. Malumbres M, Barbacid M.To cycle or not to cycle: a critical decision in cancer [J]. Nat Rev Cancer, 2001,1(3): 222-231.
2. Hwang HC, Clurman BE. Cyclin E in normal and neoplastic cell cycles [J].Oncogene, 2005, 24(17): 2776-2786.
3. Satyanarayana A, Hilton MB, Kaldis P. p21 Inhibits CDK1 in the absence of CDK2 to maintain the G1/S phase DNA damage checkpoint. Mol Biol Cell, 2008,19(1):65-77.
4. Neganova I, Zhang X, Atkinson S, et al. Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells [J]. Oncogene, 2008, 358(10): 1038.
5. Hochegger H, Dejsuphong D, Sonoda E,et al. An essential role for CDK1 in S phase control is revealed via chemical genetics in vertebrate cells. J Cell Biol,2007,178(2):257-268.
6. Krasinska L, Besnard E, Cot E, et al .CDK1 and CDK2 activity levels determine the efficiency of replication origin firing in Xenopus.EMBO J,2008,27(5):758-769.
7. Satyanarayana A, Berthet C, Lopez-Molina J, et al. Genetic substitution of CDK1 by CDK2 leads to embryonic lethality and loss of meiotic function of CDK2 [J].Development, 2008, 135(20): 3389-3400.
8. De Boer L, Oakes V, Beamish H, et al. Cyclin A/CDK2 coordinates centrosomal and nuclear mitotic events. Oncogene, 2008,27(31):4261-4268.
9. Gong D, Pomerening JR, Myers JW, et al. Cyclin A2 regulates nuclear-envelope breakdown and the nuclear accumulation of Cyclin Bl. Curr Biol, 2007,17(1):85-91.
10. Chen Q, Zhang X, Jiang Q, et al. Cyclin Bl is localized to unattached kinetochores and contributes to efficient microtubule attachment and proper chromosome alignment during mitosis. Cell Res, 2008,18(2):268-280.
11. Soni DV, Sramkoski RM, Lam M,et al . Cyclin Bl is rate limiting but not essential for mitotic entry and progression in mammalian somatic cells. Cell Cycle, 2008,7(9): 1285-1300.
12. Nigg EA. Mitotic kinases as regulators of cell division and its checkpoints[J]. Nat Rev Mol Cell Biol, 2001, 2(1): 21-32.
13. Cruz JC, Tsai LH. A Jekyll and Hyde kinase: roles for CDK5 in brain development and disease [J]. Curr Opin Neurobiol, 2004, 14(3): 390-394.
14. Kesavapany S, et al. Neuronal Cyclin-dependent kinase 5: role in nervous system function and its specific inhibition by the CDK5 inhibitory peptide.Biochim. Biophys. Acta, 2004, 1697:143-153.
15. Lolli G, Johnson LN. CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs? [J]. Cell Cycle, 2005, 4(4): 572-577.
16. Lolli G, Johnson LN. Recognition of CDK2 by CDK7. Proteins,2007,67(4):1048-1059.
17. Larochelle S, Merrick KA, Terret ME, et al . Requirements for CDK7 in the assembly of CDK1/Cyclin B and activation of CDK2 revealed by chemical genetics in human cells. Mol Cell, 2007, 25 (6):839-850.
18. Akoulitchev S,et al. TFIIH is negatively regulated by CDK8-containing mediator complexes. Nature, 2000, 407:102-106.
19. Garriga J, Grana X. Cellular control of gene expression by T-type Cyclin/CDK9 complexes [J]. Gene, 2004, 337:15-23.
20. Kasten M, Giordano A. CDK10, a Cdc2-related kinase, associates with the Ets2 transcription factor and modulates its transactivation activity [J]. Oncogene, 2001,20(15): 1832-1838.
21. Loyer P, Trembley JH, Katona R, et al. Role of CDK/Cyclin complexes in transcription and RNA splicing [J]. Cell Signal, 2005, 17(9): 1033-1051.
22. Chen HH, Wang YC, Farm MJ. Identification and characterization of the CDK12/Cyclin L1 complex involved in alternative splicing regulation [J]. Mol Cell Biol, 2006, 26(7): 2736-2745.
23. Chen HH, Wong YH, Geneviere AM, et al. CDK13/CDC2L5 interacts with L-type Cyclins and regulates alternative splicing[J].Biochem Biophys Res Commun,2007,354(3):735-740.
24.Forester CM,Maddox J,Louis JV,et al.Control of mitotic exit by PP2A regulation of Cdc25C and CDK1.Proc Natl Acad Sci U S A,2007 Dec 11;104(50):19867-19872.
25.Ruiz EJ,Hunt T,Nebreda AR.Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO,but not CDK/Cyclin,via site-specific phosphorylation[J].Mol Cell,2008,32(2):210-220.
26.李志琴,章静波.细胞周期及其调控-兼论2001年诺贝尔生物学或医学奖.生理科学进展,2002,33:187.
27.Barrette BA,Srivatsa PJ,Cliby WA,et al.Overexpression of p34cdc2 protein kinase in epithelial ovarian carcinoma.Mayo Clin Proc,1997;72:925-929.
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32.Goyeneche AA,Caron RW,Telleria CM.Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo[J].Clin Cancer Res,2007,13(11):3370-3379.
33.Masciullo V,Scambia G,Marone M,et al.Altered expression of Cyclin D1 and CDK4 genes in ovarian carcinomas.Int J Cancer,1997,74:390-395.
34.Kusume T,Tsuda H,Kawabata M,et al.The p16-Cyclin D1/CDK4-pRb pathway and clinical outcome in epithelial ovarian cancer.Clin Cancer Res,1999,5:4152- 4157.
35.Sui L,Ding Y,Ohno M,et al.Inverse expression of CDK4 and p16 in epithelial ovarian tumors.Gynecol Oncol,2000,79:230-237.
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37.Gao N,Flynn DC,Zhang Z,et al.G1 cell cycle progression and the expression of G1 Cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells[J].Am J Physiol Cell Physiol,2004,287(2):281-291.
38.Sawiris GP,Sherman-Baust CA,Becker KG,et al.Development of a highly specialized cDNA array for the study and diagnosis of epithelial ovarian cancer [J].Cancer Res,2002,62(10):2923-2928.
2.Lindqvist A,Kallstrom H,Lundgren A,et al.CDC25B cooperates with CDC25A to induce mitosis but has a unique role in activating Cyclin B12CDK1at the centrosome[J].J Cell Biol,2005,171(1):35-45.
3.乐杰.妇产科学,2008,7:279.
4.Lolli G,Johnson LN.CAK-Cyclin-dependent Activating Kinase:a key kinase in cell cycle control and a target for drugs?[J].Cell Cycle,2005,4(4):572-577.
5.Lolli G,Johnson LN.Recognition of CDK2 by CDK7.Proteins,2007,67(4):1048-1059.
6.Forester CM,Maddox J,Louis JV,et al.Control of mitotic exit by PP2A regula tion of Cdc25C and CDK1.Proc Natl Acad Sci U S A.2007 Dec 11;104(50):19867-19872.
7.Stark GR,Taylor WR.Control of the G_2/M transition.Mol Biotechenol,2006,32:227-248.
8.De Souza CP,Ellem KA,Gabrielli BG.Centrosomal and cytoplasmic Cdc2/CyclinB1 activation precedes nuclear mitotic events[J].Exp Cell Res,2000,257(1):11-21.
9.Bonnet J,Coopman P,Morris MC.Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis.Cell Cycle,2008,7(13):1991-1998.
10.Lindqvist A,van Zon W,Karlsson Rosenthal C,et al.CyclinB1-CDK1 activation continues after centrosome separation to control mitotic progression.PLoS Biol,2007,5(5):123.
11.Nigg EA.Mitotic kinases as regulators of cell division and its checkpoints[J].Nat Rev Mol Cell Biol,2001,2(1):21-32.
12.Wong OK,Fang G.CDK1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1 mediated formation of the 3F3/2 epitope.J Cell Biol,2007,179(4):611-617.
13. Orchard C B , Siciliano I, Sorrell D A , et al. Tobacco BY-2 cells expressing fission yeast CDC25 bypass a G_2/ M block on the cell cycle[J]. The Plant Journal,2005 ,442:290-299.
14. L(?)ffler H, Rebacz B, Ho AD, et al. Chk1-dependent regulation of CDC25B functions to coordinate mitotic events. Cell Cycle, 2006,1 ;5(21 ):2543-2547.
15. Boutros R, Ducommun B. Asymmetric localization of the CDC25B phosphatase to the mother centrosome during interphase. Cell Cycle,2008 Febl;7(3):401-406.
16. Dutertre S, Cazales M , Quaranta M , et al. Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G_2 -M transition[J].J Cell Sci ,2004,117(12):2523-2531.
17. Lobjois V, Jullien D, Bouch(?) JP, et al. The polo-like kinase 1 regulates CDC25B -dependent mitosis entry. Biochim Biophys Acta, 2009,1793(3):462-468.
18. Baldin V, Pelel K, Cazales M, et al. Nuclear localization of CDC25B1 and serine 146 integrity are required for induction of mitosis[J],J Biol Chem, 2002, 277(38):35176-35182.
19. Bansal P, Lazo JS. Induction of CDC25B regulates cell cycle resumption after genotoxic stress. Cancer Res, 2007,67(7):3356-3363.
20. Aressy B, Ducommun B. Cell cycle control by the CDC25 phosphatases. Anticancer Agents Med Chem, 2008 ,8(8):818-824.
21. Kramer A , Mailand N , Lukas C, et al. Centrosome-associated Chkl prevents premature activation of Cyclin2B2CDKl kinase[J ].Nat,Cell Biol,2004,6(9):884-891.
22. Santamaria D, Barri(?)re C, Cerqueira A,et al. CDKl is sufficient to drive the mammalian cell cycle. Nature, 2007 ,448(7155):811-815.
23. Willim K, Richard SP. DNA damaged and cell cycle checkpoint s.The FASEB [J],1996,10:238.
24. Khandan K,Arthur BP. Redundant Cyclin over expression and gene amplication in breast cancer cells. Pro Natl Acad Sci USA,1993,90:1112.
25. Juliano R.Movin' on through with Cdc2. Nat Cell Biol ,2003,5:589-590.
26. Liu P, Kao TP, Huang H. CDK1 promotes cell proliferation and survival via phosphorylation and inhibition of FOXO1 transcription factor. Oncogene,2008,27 (34):4733-4744.
27. Senju M ,Sueoka N,Satato A,et al. Hsp90 inhibitors cause G_2/M arrest associated with the reductionof Cdc25C and Cdc2 in lung cancer cell lines[J ]. J Cancer Res Clin Oncol ,2006,132 (3): 150-158.
28. Banerjee SK,Weston AP,Zoubine MN ,et al. Expression of cdc2 and CyclinBl in helicobacter pylori associated gastric MALT and MALT lymphoma: relationship to cell death , proliferation ,and transformation [J]. Am J Pathol ,2000,156(1):217-225.
29. Sarela AI,Verbeke CS,Ramsdale J ,et al. Expression of survivin ,a novel inhibitor of apoptosis and cell cycle regulatory protein ,in pancreatic adenocarcinoma [J].Br J Cancer ,2002 ,86(6):886-892.
30. Welsh JB, Zarrinkar PP, Sapinoso LM, et al. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer [J]. Proc Natl Acad Sci USA, 2001,98(3):1176-1181.
31. Chen H, Huang Q, Zhai DZ,et al.CDK1 expression and effects of CDK1 silencing on the malignant phenotype of glioma cells.Zhonghua Zhong Liu Za Zhi, 2007,29 (7):484-488.
32. Kourea HP, Koutras AK, Scopa CD, et al. Expression of the cell cycle regulatory protein p34cdc2, p21waf1, and p53 in node negative invasive ductal breast carcino ma.M ol Pathol, 2003,56:328-335.
33. Kim SJ, Nakayama S, Miyoshi Y, et,al. Determination of the specific activity of CDK1 and CDK2 as a novel prognostic indicator for early breast cancer. Ann Oncol, 2008,19:68-72.
34. NozoeT, Honda M , Inutsuka S, etal. P34cdc2 expression is an independent indicator for lymph node metastasis in colorectal carcinoma.Cancer Res Clin Oricof, 2003,129:498-502.
35. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm.Nat Rev Cancer, 2009,9(3): 153-166.
36. Warenius HM, Seabra L, Kyritsi L, et al. Theranostic proteomic profiling of Cyclins, Cyclin dependent kinases and Ras in human cancer cell lines is dependent on p53 mutational status. Int J Oncol, 2008,32(4):895-907.
37. Nakayama S, Torikoshi Y, Takahashi T, et al. Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells. Breast Cancer Res,2009,11(1):12.
38. Beatrix B, Muriel Q, Bernadette A.Genotoxic-activated G_2-M checkpoint exit is dependent on CDC25B phosphatase expression. Mol Cancer Ther, 2006,5:1446-1451.
39. Srivastava SK, Bansal P, Oguri T,et,al.Cell division cycle 25B phosphatase is essential for benzo(a)pyrene-7,8-Diol-9,10-epoxide induced neoplastic transfor mation. Cancer Res, 2007, 67: 9150-9157 .
40. Boutros R, Lobjois V, Ducommun B. CDC25B involvement in the centrosome duplication cycle and in microtubule nucleation. Cancer Res, 2007,67:11557-11564.
41. Lazo J S, Nemoto K, Pestell K E, et al. Identification of a potent and selective pharmacophore for CDC25 dual specificity phosphatase inhibitors[J]. Mol Pharmacol, 2002, 61(4):720-728.
42. Lazo J S, Asian D C, Southwick E C, et al. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase CDC25[J ]. J Med Chem, 2001,44(24):4042-4049.
43. Sodeoka M , Sampe R , Kojima S, et al. Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR andCDC25B inhibition[J]. Med Chem, 2001, 44(20):3216-3222.
44. Varmeh S, Manfredi JJ. Inappropriate activation of Cyclin-dependent kinases by the phosphatase CDC25B results in premature mitotic entry and triggers a p53-dependent checkpoint. J Biol Chem, 2009,45(2):32-36.
45. Broggini M, Buraggi G, Brenna A, et al. Cell cycle related phosphatases CDC25A and B expression correlates with survival in ovarian cancer patients [J].Anticancer Res,2000,20 (60):4835-4840.
46. Takemasa I,Yamamoto H,Sekimoto M,et al. Overexpression of CDC25B phosphatase as a novel marker of poor prognosis of human colorectal carcinoma [J].CancerRes,2000,60(11):3043-3050.
47. Boldrini L, Gisfredi S, Ursino S, et al. CDC25B: relationship with angiogenesis and prognosis in non-small cell lung carcinoma. Hum Pathol, 2007,38(10): 1563-1568.
48. Aressy B, Bugler B, Valette A, et al. Moderate variations in CDC25B protein levels modulate the response to DNA damaging agents. Cell Cycle, 2008,7(14):2234-2240.
49. Chen RQ, Yang QK, Lu BW, et al. CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res, 2009,69(6):2663-2668.
50. Varmeh-Ziaie S, Manfredi JJ. The dual specificity phosphatase CDC25B, but not the closely related Cdc25C, is capable of inhibiting cellular proliferation in a manner dependent upon its catalytic activity. J Biol Chem,2007,282(34):24633-24641.
51. Galaktinov K, Lee AK, Eckstein J, et al. cdc25 cell-cycle phosphatase as potential human oncogenesis. Science ,1995,269:1575-1577.
52. Boutros R, Lobjois V, Ducommun B. CDC25B involvement in the centrosome duplication cycle and in microtubule nucleation. Cancer Res,2007,67(24):11557-11564.
1. Malumbres M, Barbacid M.To cycle or not to cycle: a critical decision in cancer [J]. Nat Rev Cancer, 2001,1(3): 222-231.
2. Hwang HC, Clurman BE. Cyclin E in normal and neoplastic cell cycles [J].Oncogene, 2005, 24(17): 2776-2786.
3. Satyanarayana A, Hilton MB, Kaldis P. p21 Inhibits CDK1 in the absence of CDK2 to maintain the G1/S phase DNA damage checkpoint. Mol Biol Cell, 2008,19(1):65-77.
4. Neganova I, Zhang X, Atkinson S, et al. Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells [J]. Oncogene, 2008, 358(10): 1038.
5. Hochegger H, Dejsuphong D, Sonoda E,et al. An essential role for CDK1 in S phase control is revealed via chemical genetics in vertebrate cells. J Cell Biol,2007,178(2):257-268.
6. Krasinska L, Besnard E, Cot E, et al .CDK1 and CDK2 activity levels determine the efficiency of replication origin firing in Xenopus.EMBO J,2008,27(5):758-769.
7. Satyanarayana A, Berthet C, Lopez-Molina J, et al. Genetic substitution of CDK1 by CDK2 leads to embryonic lethality and loss of meiotic function of CDK2 [J].Development, 2008, 135(20): 3389-3400.
8. De Boer L, Oakes V, Beamish H, et al. Cyclin A/CDK2 coordinates centrosomal and nuclear mitotic events. Oncogene, 2008,27(31):4261-4268.
9. Gong D, Pomerening JR, Myers JW, et al. Cyclin A2 regulates nuclear-envelope breakdown and the nuclear accumulation of Cyclin Bl. Curr Biol, 2007,17(1):85-91.
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