细胞周期素G1和G2在膀胱癌中的表达及临床意义

目的探讨细胞周期素G1和G2在膀胱移行细胞癌（尿路上皮癌）中的表达及临床意义。方法收集武汉大学人民医院病理科2000-2006年有完整临床和病理资料的膀胱移行细胞癌存档蜡块50例和5例癌旁组织,采用免疫组织化学S-P法检测50例膀胱移行细胞癌和5例癌旁组织中细胞周期素G1和G2的表达水平。采用HPIAS-1000高清晰度彩色病理图文报告管理系统,对细胞周期素G1和G2的表达进行定量分析,并用SPSS11.5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验。结果细胞周期素G1在膀胱移行细胞癌中呈高表达,癌旁组织中呈低表达。而细胞周期素G2在膀胱移行细胞癌中呈低表达,癌旁组织中呈高表达。膀胱移行细胞癌与癌旁组织相比,差异有显著性（P〈0.05）。随着移行细胞癌组织中细胞周期素G1表达的增高,周期素G2的表达却显著下降,两者呈显著负相关（P〈0.01）。结论细胞周期素G1和G2在膀胱移行细胞癌与癌旁组织中对细胞周期调控和/或DNA修复起了重要作用,并参与了诱导细胞凋亡的过程。     

p27^kip1及相关分子skp2在肺癌组织中的表达及其临床意义

目的：研究细胞周期素依赖性激酶抑制蛋白27（p27^kip1）和细胞S相激酶相关蛋白2（skp2）在肺癌癌组织中的表达及意义。方法：选取于我院就诊的72例肺癌患者的肺癌组织和20例癌旁正常肺组织,采用免疫组化技术检测标本中p27^kip1和skp2的表达,并分析其与患者的临床病理之间的关系。结果：skp2在肺癌组织中的表达高于正常肺组织,而p27^kip1在肺癌组织中的表达低于正常肺组织,差异均有统计学意义（P〈0.05）,且两者的表达呈负相关关系,相关系数r=-0.855（P〈0.05）,skp2的表达与肺癌组织学类型、分化程度、TNM分期、淋巴结有无转移、吸烟与否及p27^kip1蛋白表达有关（P〈0.05）。结论：p27^kip1低表达和skp2高表达可能是肺癌发生发展的重要原因,可应用于临床诊治肺癌患者和判断预后。     

胃癌、癌旁和正常组织中存活蛋白的表达与细胞周期变化的相关性研究

目的:探讨胃癌、癌旁和正常组织中存活蛋白的表达情况及其与细胞周期变化的相关性。方法:采用免疫组化SP法检测胃癌、癌旁和正常组织中存活蛋白的表达,同时用流式细胞仪检测3种组织中细胞周期的变化,分析存活蛋白的表达与细胞周期变化的相关性。结果:存活蛋白在正常胃黏膜组织中无表达,胃癌癌旁组织中阳性表达率为16.67%,胃癌组织中阳性表达率为46.67%;与正常胃组织比较,胃癌癌旁组织和胃癌组织G0/G1期细胞均有明显下降,S期细胞均有明显升高,胃癌组织G2/M期细胞明显高于正常组织;存活蛋白的表达与G2/M期细胞数相关(rs=0.627)。结论:存活蛋白在胃癌组织中表达明显增加,并且与胃癌组织细胞周期变化相关,可通过调节细胞周期促进细胞增殖。     

p27~(kip1)及相关分子skp2在肺癌组织中的表达及其临床意义

目的:研究细胞周期素依赖性激酶抑制蛋白27(p27kip1)和细胞S相激酶相关蛋白2(skp2)在肺癌癌组织中的表达及意义。方法:选取于我院就诊的72例肺癌患者的肺癌组织和20例癌旁正常肺组织,采用免疫组化技术检测标本中p27kip1和skp2的表达,并分析其与患者的临床病理之间的关系。结果:skp2在肺癌组织中的表达高于正常肺组织,而p27kip1在肺癌组织中的表达低于正常肺组织,差异均有统计学意义(P0.05),且两者的表达呈负相关关系,相关系数r=-0.855(P0.05),skp2的表达与肺癌组织学类型、分化程度、TNM分期、淋巴结有无转移、吸烟与否及p27kip1蛋白表达有关(P0.05)。结论:p27kip1低表达和skp2高表达可能是肺癌发生发展的重要原因,可应用于临床诊治肺癌患者和判断预后。     

细胞信号分子Tiaml和Racl在膀胱尿路上皮癌中的表达及意义

目的 探讨细胞信号分子Tiaml和Racl在膀胱尿路上皮癌中的表达及临床意义.方法 收集武汉大学人民医院病理科2006-2010年有完整临床和病理资料的膀胱尿路上皮癌存档蜡块50例和5例癌旁组织,采用免疫组织化学S-P法检测50例膀胱尿路上皮癌和5例癌旁组织中Tiaml和Racl的表达水平.应用彩色病理图文报告管理系统,对Tiaml和Racl的表达进行定量分析,并用SPSS13.0 软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验.结果 （1）Tiaml的表达 Tiaml在膀胱尿路上皮癌中呈高表达,而在癌旁组织中呈低表达.膀胱尿路上皮癌与癌旁组织相比,差异有显著性 （P〈0.05 ）;（2）Racl的表达 Racl在膀胱尿路上皮癌中呈高表达,而在癌旁组织中呈低表达.膀胱尿路上皮癌与癌旁组织相比,差异有显著性 （P〈0.05 ）;（3）膀胱尿路上皮癌中Tiaml与Racl的表达呈正相关,它们相互作用、相互调控.结论 Tiaml和Racl在膀胱尿路上皮癌中的表达异常可能是膀胱尿路上皮癌的早期分子事件,在膀胱尿路上皮癌的发生和发展中发挥了重要作用,并Tiaml与Racl的表达呈正相关,它们相互作用、相互调控,在膀胱尿路上皮癌的发生、发展过程中,两者起协同作用.     

ADO在膀胱尿路上皮癌组织中的表达和意义

目的探讨膀胱尿路上皮癌组织中腺苷(adenosine,ADO)的表达及临床意义。方法收集武汉大学人民医院病理科2000-2006年有完整临床和病理资料的膀胱尿路上皮癌存档蜡块50例和5例癌旁组织,采用免疫组织化学S-P法检测50例膀胱尿路上皮癌和5例癌旁组织中ADO的表达水平。采用HPIAS-1000高清晰度彩色病理图文报告管理系统,对ADO的表达进行定量分析,并用SPSS13.0软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK(q)检验。结果 ADO在膀胱尿路上皮癌中呈低表达,癌旁组织中呈高表达。膀胱尿路上皮癌与癌旁组织相比,差异有显著性(P<0.05)。结论 ADO在膀胱尿路上皮癌中的低表达抑制了肿瘤细胞的凋亡,导致肿瘤细胞增生,ADO在膀胱尿路上皮癌的发生、发展中起了重要的促进作用。     

CBX7蛋白在甲状腺乳头状癌中的表达及意义

目的探讨CBX7蛋白在甲状腺乳头状癌组织中的表达及其临床意义。方法收集江夏区人民医院病理科2009-2013年手术切除及活检的甲状腺乳头状癌标本40例和癌旁组织标本20例。采用免疫组织化学方法检测各组组织中CBX7蛋白的表达。并对各组免疫组织化学反应的平均光密度和平均阳性面积率做单因素方差分析和SNK(q)检验,检验水准α为0.05。结果 CBX7蛋白在癌旁组织中呈高表达,甲状腺乳头状癌中呈低表达,统计分析显示,CBX7蛋白在癌旁组织中的表达显著高于甲状腺乳头状癌(P0.05)。结论 CBX7蛋白在甲状腺乳头状癌中呈低表达,可能与甲状腺乳头状癌的发生和发展密切相关。     

抑癌基因DPC4和TGF-β1在膀胱尿路上皮癌中的表达和意义

目的探讨膀胱尿路上皮癌中TGF-β1和DPC4的表达及其意义。方法收集武汉大学人民医院病理科2000-2006年有完整临床和病理资料的膀胱尿路上皮癌存档蜡块50例和5例癌旁组织,采用免疫组织化学S-P法检测50例膀胱与癌旁组织相比,差异有显著性(P<0.05);(2)DPC4在膀胱尿路上皮癌中呈低表达,癌旁组织中呈高表达。膀胱尿路上皮尿路上皮癌和5例癌旁组织中DPC4和TGF-β1的表达水平。采用HPIAS-1000高清晰度彩色病理图文报告管理系统,对DPC4和TGF-β1的表达进行定量分析,并用SPSS13.0软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK(q)检验。结果 (1)TGF-β1在膀胱尿路上皮癌中呈高表达,癌旁组织中呈低表达。膀胱尿路上皮癌癌与癌旁组织相比,差异有显著性(P<0.05)。结论 TGF-β1高表达和DPC4低表达可能促进肿瘤细胞发生免疫逃逸。在膀胱尿路上皮癌的发生和发展中发挥了重要作用。     

D类细胞周期素在细胞周期中的作用

细胞周期进程由周期性表达的细胞周期素和细胞周期素信号性激酶推动完成,CyclinD在G1期中期开始表达,是最早合成的细胞周期素,它与Cdk4或Cdk6形成的活性复合物,不仅可促进pRb的磷酸化,也可隔离P27对cyclinE-Cdk2活性的抑制,使细胞顺利越过G1期进入S期,除此之外,cyclinD过度表达还可抑制细胞增殖,在细胞分化和衰老过程中发挥重要作用。     

Pirh2和P27kip1蛋白在肺癌中的表达及其临床意义

目的探讨pirh2、p27Kip1在肺癌和癌旁组织中表达的相关性及其与肿瘤发生发展的关系。方法应用免疫组织化学S-P法检测53例肺癌和17例癌旁石蜡包埋存档标本组织中pirh2和p27kip1蛋白的表达,并对其所在肺癌组织不同病理类型、分级、和临床分期及转移中的表达水平进行对统计学分析。结果pirh2蛋白在肺癌组织中呈高表达,表达率为79.2%,P27Kip1蛋白呈低表达,为22.6%,二者与癌旁组织相比(阳性表达率分别为11.8%和64.7%),差异具有显著性意义(P<0.01),但是二者与肿瘤的病理类型、组织学分级、淋巴结转移和TNM分期均无明显相关关系(P>0.05)。Pirh2表达阳性的肺癌组织中,p27Kip1的阳性率较低,二者呈显著负相关。结论pirh2过表达和p27Kip1蛋白的低表达可促进肿瘤的发生;二者之间呈负性相关关系,提示降解p27Kip1蛋白可能是pirh2促进肿瘤形成的途径之一。     

食管鳞状细胞癌中DICKKOPF-3基因的甲基化状态及表达

目的检测食管鳞状细胞癌(esophageal squamous cell cancer,ESCC)中Wnt通路拮抗基因DICKKOPF-3(DKK3)的甲基化状态,探讨其与ESCC发生的关系。方法应用甲基化特异性PCR(methylation specificPCR,MSP)及RT-PCR的方法检测78例ESCC及相应癌旁非肿瘤组织中DKK3基因的甲基化状态及mRNA表达情况,应用免疫组化的方法检测通路中心因子-βcatenin蛋白及下游靶基因cyclinD1的表达,并分析其与食管癌发生的关系。结果在ESCC组织中,DKK3基因的甲基化频率为37.2%(29/78),明显高于癌旁非肿瘤组织(χ2=35.622,P=0.000);癌组织中该基因的甲基化率与肿瘤患者临床分期相关(χ2=4.705,P=0.030),而与组织学分级无关;食管癌中DKK3基因mRNA的阳性表达率为65.4%(51/78),明显低于癌旁非肿瘤组织(χ2=13.298,P=0.000)。在发生甲基化的食管癌组织中该基因的mRNA表达缺失及-βcatenin蛋白的异质表达率均明显高于未发生甲基化的癌组织,且差异有统计学意义(χ2mRNA=29.141,P=0.000;χ2-βcatenin=6.245,P=0.012)。食管癌中cyclinD1的表达明显高于癌旁组织,且癌组织中该蛋白的表达与DKK3基因的甲基化状态相关(χ2=4.921,P=0.027)。结论 ESCC组织中DKK3基因高甲基化导致的转录沉默可能与食管癌的发生有关,并可能通过活化Wnt/-βcatenin信号转导通路促进下游靶基因cyclinD1的过表达发挥作用。     

RNA干扰Ｃyclin D1基因表达对瘢痕疙瘩成纤维细胞增殖和G1期调控的影响

为研究siRNA干扰瘢痕疙瘩成纤维细胞cyclin D1基因表达,对瘢痕疙瘩成纤维细胞的增殖、细胞周期和G1期调控的影响,构建了靶向cyclin D1的siRNA表达质粒.利用LipofecmmineTM2000转染体外培养的瘢痕疙瘩成纤维细胞,应用荧光定量PCR、RT-PCR检测cyclin D1 mRNA的干扰效果,应用MTT法、流式细胞仪检测细胞增殖和细胞周期的变化,应用免疫组织化学染色检测成纤维细胞中cyclin D1、CDK4、P16、pRb蛋白表达的影响.主要结果如F:a.靶向cyclin D1的特异性siRNA序列可以高效地抑制成纤维细胞cyclin D1基因表达,对照组与实验组在mRNA水平其表达抑制率分别为63.68%和92.83%(P<0.01);b.可以显著抑制瘢痕疙瘩成纤维细胞的增殖,改变细胞周期分布,G0/G1期细胞比例显著高于各对照组(P<0.05),细胞分裂被阻滞;c.免疫组化染色发现,转染72 h后,过表达的cyclin D1、CDK4和pRb蛋白,在瘢痕疙瘩成纤维细胞中均出现了不同程度的表达下调,而低表达的P16则呈上调表现.由上述结果可见,构建的靶向cyclin D1的RNAi表达质粒,可有效地抑制瘢痕疙瘩成纤维细胞cyclin D1基因表达,通过改变Gl期相关周期蛋白的水平,影响G1/S期的进程,显著地抑制成纤维细胞的增殖.     

WWOX蛋白在胰腺癌组织中的表达及其临床意义

目的探讨WWOX蛋白在胰腺癌组织中的表达及其临床意义。方法应用免疫组织化学孓P法检测人胰腺癌组织芯片150芯（包括70例胰腺癌组织和5例胰腺炎）中WWOX蛋白的表达,采用HPIAS-1000图文报告管理系统对WWOX蛋白的表达进行定量分析,并用SPSS11．5软件对各组免疫组织化学反应阳性颗粒的平均光密度、阳性面积率做单因素方差分析和SNK（q）检验。结果胰腺癌组织中WWOX蛋白呈低表达,胰腺炎组织中WWOX蛋白呈高表达。结论提示WWOX基因表达下调可能在胰腺癌的发生、发展中起了重要作用。     

MiR-23a-3p promoted G1/S cell cycle transition by targeting protocadherin17 in hepatocellular carcinoma

MiR-23a-3p has been shown to promote liver cancer cell growth and metastasis and regulate that of chemosensitivity. Protocadherin17 (PCDH17) is a tumor suppressor gene and plays an essential part in cell cycle of hepatocellular carcinoma (HCC). This study aimed at evaluating the effects of miR-23a-3p and PCDH17 on HCC cell cycle and underlining the mechanism. The level of miR-23a-3p was up-regulated, while PCDH17 level was down-regulated in HCC tissues compared to adjacent tissues. For the in vitro studies, high expression of miR-23a-3p down-regulated PCDH17 level; increased cell viability; promoted G1/S cell cycle transition; up-regulated cyclin D1, cyclin E, CDK2, CDK4, p-p27, and p-RB levels; and down-regulated the expression of p27. Dual luciferase reporter assay suggested PCDH17 was a target gene of miR-23a-3p. MiR-23a-3p inhibitor and PCDH17 siRNA led to an increase in cell viability and the number of cells in the S phase and up-regulated cyclin D1 and cyclin E levels, compared with miR-23a-3p inhibitor and NC siRNA group. For the in vivo experiments, high expression of miR-23a-3p promoted tumor growth and reduced PCDH17 level in the cytoplasm. These results indicated that high expression of miR-23a-3p might promote G1/S cell cycle transition by targeting PCDH17 in HCC cells. The miR-23a-3p could be considered as a molecular target for HCC detection.

     

G6PD通过细胞周期蛋白D1/D2调控人黑色素瘤细胞周期的进程

葡萄糖-6-磷酸脱氢酶(G6PD)在人皮肤黑色素瘤A375细胞中处于高表达与高活性状态, 但G6PD在黑色素瘤发生发展过程中的作用及其具体机制尚不明确.本文在前期运用 siRNA方法构建G6PD敲减的黑色素瘤A375稳转细胞(A375-G6PDΔ)基础上,构建表达载体pBabe-puro-G6PDWT在A375-G6PDΔ细胞中过表达野生型的G6PD基因,从而构建G6PD表达恢复的稳转细胞(A375-G6PDΔ-G6PDWT).3株细胞A375-WT、A375-G6PDΔ和 A375-G6PDΔ-G6PDWT经G6PD酶活性测定、MTT测定、克隆形成实验、流式细胞仪分析细胞周期和Western 印迹检测.结果显示,A375-G6PDΔ-G6PDWT细胞的G6PD蛋白表达量 (0.847 ± 0.080)及其活性(0.394 ± 0.029)分别是A375-G6PDΔ的3.28倍(P＜0.01) 和7.34倍(P＜0.01),分别是A375-WT细胞的91-57%和2.12倍(P＜0.05).与A375-WT细 胞相比,A375-G6PDΔ细胞G0/G1期细胞数增加,S期细胞数减少,增殖指数PI降低了25-70%（P＜0.05）,细胞周期蛋白D1/D2、细胞周期蛋白E表达分别下降37.4%、54.3% (P＜0.01)和17.3%;而A375-G6PDΔ-G6PDWT细胞呈现G1/S期阻滞解除,细胞周期蛋白D1/D2蛋白分别恢复到A375-WT细胞的89.5%和87.6%,细胞周期蛋白E表达未见 恢复,呈现生长增殖和克隆形成率的恢复并接近于A375-WT细胞. 结果提示,G6PD通 过细胞周期蛋白D1/D2调控人皮肤黑色素瘤A375细胞G1期向S期转换的进程,这为黑色 素瘤发病机制的研究提供了新的思路.     

NGX6基因对人结肠癌细胞HT-29细胞周期的影响

NGX6基因是新克隆的候选抑瘤基因,研究表明NGX6重表达可抑制结肠癌细胞的增殖.为进一步研究NGX6对细胞周期的影响,采用流式细胞仪检测NGX6重表达对结肠癌细胞HT-29细胞周期的影响,发现NGX6重表达可增加HT-29细胞在G0/G1期的分布比例,减少了S,G2,M期细胞数.利用蛋白质印迹和流式细胞术分析NGX6转染前后HT-29细胞周期素(cyclins)和细胞周期素依赖性蛋白激酶抑制物(cyclin-dependentkinaseinhibitor,CKI)的表达变化,发现NGX6可下调HT-29细胞中cyclinE、cyclinD1的表达及上调p27的表达,对cyclinA和cyclinB的表达无明显影响,p16在三组结肠癌细胞中均无表达.研究结果表明,NGX6在HT-29细胞中通过下调cyclinE、cyclinD1和上调p27的表达,阻滞细胞周期于G0/G1期,从而发挥其在结肠癌中的抑瘤作用.     

Overexpression of TRIM24 correlates with tumor progression in non-small cell lung cancer

The objective of the current study was to investigate the expression pattern and clinicopathological significance of TRIM24 in patients with non-small cell lung cancer (NSCLC). The expression profile of TRIM24 in NSCLC tissues and adjacent noncancerous lung tissues was detected by immunohistochemistry. TRIM24 was found to be overexpressed in 81 of 113 (71.7%) human lung cancer samples and correlated with p-TNM stage (p = 0.0006), poor differentiation (p = 0.004), Ki67 index (p<0.0001), cyclin D1(p = 0.0096) and p-Rb expression (p = 0.0318). In addition, depleting TRIM24 expression by small interfering RNA inhibited growth and invasion in lung cell lines. Moreover, TRIM24 depletion induced cell cycle arrest at the G1/S boundary and induced apoptosis. Western blotting analysis revealed that knockdown of TRIM24 decreased the protein levels of Cyclin A, Cyclin B, Cyclin D1, cyclin E and p-Rb and increased P27 expression. These results indicate that TRIM24 plays an important role in NSCLC progression.     

PDK1 regulates cell proliferation and cell cycle progression through control of cyclin D1 and p27Kip1 expression

PDK1 (3-phosphoinositide-dependent protein kinase 1) is a key mediator of signaling by phosphoinositide 3-kinase. To gain insight into the physiological importance of PDK1 in cell proliferation and cell cycle control, we established immortalized mouse embryonic fibroblasts (MEFs) from mice homozygous for a "floxed" allele of Pdk1 and from wild-type mice. Introduction of Cre recombinase by retrovirus-mediated gene transfer resulted in the depletion of PDK1 in Pdk1(lox/lox) MEFs but not in Pdk1(+/+) MEFs. The insulin-like growth factor-1-induced phosphorylation of various downstream effectors of PDK1, including Akt, glycogen synthase kinase 3, ribosomal protein S6, and p70 S6 kinase, was markedly inhibited in the PDK1-depleted (Pdk1-KO) MEFs. The rate of serum-induced cell proliferation was reduced; progression of the cell cycle from the G(0)-G(1) phase to the S phase was delayed, and cell cycle progression at G(2)-M phase was impaired in Pdk1-KO MEFs. These cells also manifested an increased level of p27(Kip1) expression and a reduced level of cyclin D1 expression during cell cycle progression. The defect in cell cycle progression from the G(0)-G(1) to the S phase in Pdk1-KO MEFs was rescued by forced expression of cyclin D1, whereas rescue of the defect in G(2)-M progression in these cells required both overexpression of cyclin D1 and depletion of p27(Kip1) by RNA interference. These data indicate that PDK1 plays an important role in cell proliferation and cell cycle progression by controlling the expression of both cyclin D1 and p27(Kip1).     

Ectopic expression of cyclin D1 but not cyclin E induces anchorage-independent cell cycle progression.

Normal fibroblasts are dependent on adhesion to a substrate for cell cycle progression. Adhesion-deprived Rat1 cells arrest in the G1 phase of the cell cycle, with low cyclin E-dependent kinase activity, low levels of cyclin D1 protein, and high levels of the cyclin-dependent kinase inhibitor p27kip1. To understand the signal transduction pathway underlying adhesion-dependent growth, it is important to know whether prevention of any one of these down-regulation events under conditions of adhesion deprivation is sufficient to prevent the G1 arrest. To that end, sublines of Rat1 fibroblasts capable of expressing cyclin E, cyclin D1, or both in an inducible manner were used. Ectopic expression of cyclin D1 was sufficient to allow cells to enter S phase in an adhesion-independent manner. In contrast, cells expressing exogenous cyclin E at a level high enough to overcome the p27kip1-imposed inhibition of cyclin E-dependent kinase activity still arrested in G1 when deprived of adhesion. Moreover, expression of both cyclins D1 and E in the same cells did not confer any additional growth advantage upon adhesion deprivation compared to the expression of cyclin D1 alone. Exogenously expressed cyclin D1 was down-regulated under conditions of adhesion deprivation, despite the fact that it was expressed from a heterologous promoter. The ability of cyclin D1-induced cells to enter S phase in an adhesion-independent manner disappears as soon as cyclin D1 proteins disappear. These results suggest that adhesion-dependent cell cycle progression is mediated through cyclin D1, at least in Rat1 fibroblasts.     

Cyclin A but not cyclin D1 is essential for c-myc-modulated cell-cycle progression

The proto-oncogene c-myc is a key player in cell-cycle regulation and is deregulated in a broad range of human cancers and cell proliferation disorders. Here we reported that overexpression of c-myc in human embryonic lung fibroblasts (HEL) that have low endogenous c-myc enriched S phase cells with increased expression of cyclin D3, E, A, Cdk2, and Cdk4, and decreased expression of p21 and p27. To the opposite, using RNAi to downregulate c-myc expression in A549 cells that have high endogenous c-myc enriched G1 phase cells with decreased expression of cyclin D3, E, A, Cdk2, Cdk4, and increased expression of p21 and p27. We found that cyclin A expression was the most susceptive to changes in c-myc levels and essential in c-myc-modulated cell cycle pathway via co-transfection, however, cyclin D1 showed no change between treated and control groups in either HEL or A549 cells. Our results indicated that upregulation of c-myc expression promotes cell cycling in HEL cells, whereas downregulation of c-myc expression causes G1 phase arrest in A549 cells, and the c-myc-mediated cell-cycle regulation pathway was dependent on cyclin A and involved cyclin D3, E, Cdk2, Cdk4, p21, and p27, but not cyclin D1.