肾癌中cyclinD1和p27kip1的表达及其意义

目的探讨cyc lin D1、p27k ip1在普通型肾细胞癌(renal cell carc inom a,RCC)发生、发展中的作用。方法用半定量RT-PCR方法检测25例普通型RCC和10例肿瘤远端的正常肾组织中cyc lin D1的mRNA含量,用免疫组化方法检测76例普通型RCC中cyc lin D1和p27k ip1蛋白的表达,并对cyc lin D1、p27k ip1蛋白表达与临床病理参数的关系进行分析。结果普通型RCC中cyc lin D1的mRNA含量0.488±0.399,高于正常对照组0.089±0.066(P<0.01)。cyc lin D1的表达与肿瘤体积大小有关,体积大者cyc lin D1高表达(P<0.05)。普通型RCC中p27k ip1表达低于正常对照组,随着p27k ip1表达的降低,肿瘤的细胞核Fu-hrm an分级、TNM分期增高。结论cyc lin D1高表达和p27k ip1的低表达与普通型RCC的发生有关;p27k ip1的低表达可能促进肿瘤的演进,p27k ip1的表达可作为评价普通型RCC预后的参考指标。     

Differential expression of cdk inhibitors p16, p21cip1, p27kip1, and cyclin E in cervical cytological smears prepared by the ThinPrep method

Our objective was to correlate p16, p21cip1, p27kip1, and cyclin E protein expression with the degree of dysplasia on ThinPrep Papanicolaou (Pap) smears using a modified immunoperoxidase staining. Smears read as normal, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or high-grade SIL (HSIL) were identified and tested for high-risk human papillomavirus (HR-HPV). Additional smears were processed for immunoperoxidase for p16, p21cip1, p27kip1, and cyclin E. Thirty-four smears were satisfactory for study. The p16 was positive in all nine HSIL, in four of nine LSIL, and in one of seven ASC-US. The p27kip1 was positive in all nine HSIL, in eight of nine LSIL, and in one of seven ASC-US. The p21cip1 was positive in all nine HSIL, in one of nine LSIL, and in one of seven ASC-US. Cyclin E was positive in seven of nine HSIL and in one of nine LSIL and in none of the ASC-US smears. Normal smears were negative for all the antigens. There was poor correlation of protein expression and HR-HPV infection. We concluded that p16, p21cip1, p27kip1, and cyclin E can be demonstrated on Pap smears and they are expressed differentially in dysplastic cells, with highest expression in HSIL. The p21cip1 and cyclin E showed the greatest correlation with HSIL.     

12(S)-HETE对大鼠系膜细胞和肾小球内p27~(kip1)表达的影响

目的:探讨12-脂氧化酶的活性代谢产物12(S)-HETE对系膜细胞和肾小球内p27~(kip1)表达的影响.方法:12(S)-HETE刺激的系膜细胞和皮下包埋的微型渗透泵长期持续恒速注入12(S)-HETE刺激的大鼠提取的肾小球来观察p27~(kip1)的表达.采用总蛋白量/细胞数的比值作为细胞肥大的评价指标,利用RT-PCR和Western blot方法检测p27~(kip1) mRNA和蛋白的表达.结果:12(S)-HETE刺激能够直接诱导系膜细胞发生肥大.12(S)-HETE刺激的系膜细胞内p27~(kip1)mRNA水平没有变化,而p27~(kip1)蛋白的表达明显增加.然而,在微型渗透泵持续恒速注入12(S)-HETE刺激的大鼠提取的肾小球内p27kip1mRNA水平和蛋白的表达均增加.结论:12(S)-HETE能够通过促进p27~(kip1)的高表达而参与细胞周期的调控,是引起肾小球系膜细胞和肾小球肥大、衰老的重要原因之一.     

stathmin和P27kip1在大肠癌中的表达及意义

目的:探讨stathmin蛋白与p27kip1蛋白在大肠癌组织中的表达及意义.方法:应用免疫组织化学SABC法检测25例正常大肠黏膜组织、25例大肠腺瘤组织、47例大肠癌组织中stathmin蛋白及p27kip1蛋白的表达情况.结果:①stathmin蛋白在正常大肠黏膜组织、大肠腺瘤组织及大肠癌组织中的阳性表达率分别为20％、48％、74.47％;正常大肠黏膜组分别与大肠腺瘤组及大肠癌组比较,差异均有统计学意义(P＜0.05);大肠腺瘤组与大肠癌组比较,差异亦有统计学意义(P＜0.05):stathmin蛋白的表达与肿瘤的分化程度、有无淋巴结转移及TNM分期显著相关(P＜0.05).②p27kap1蛋白在正常大肠黏膜组织、大肠腺瘤组织及大肠癌组织中的阳性表达率分别为92％、80％、31.91％.正常大肠黏膜组与大肠癌组比较,差异有统计学意义(P＜0.05);大肠腺瘤组与大肠癌组比较,差异亦有统计学意义(P＜0.05);正常大肠黏膜组与大肠腺瘤组比较,差异无统计学意义(P＞ 0.05);p27kip1蛋白的表达与肿瘤的分化程度及淋巴结转移有关(P＜0.05).③stathmin蛋白的表达与p27kip1蛋白的表达呈负相关(r=--0.695 3,P＜0.01).结论:stathmin蛋白在大肠癌组织中高表达,其表达程度与肿瘤的分化程度、淋巴结转移及TNM分期显著相关,p27kip1蛋白在大肠癌组织中低表达,其表达程度与肿瘤的分化程度及淋巴结转移显著相关,提示stathmin及p27kip1蛋白共同参与了大肠癌的发生、发展;stathmin蛋白可作为一种判断大肠癌恶性程度及侵袭转移的生物学指标.     

Skp2和p27kip1与肿瘤间关系的研究进展

目的：探讨Skp2和p27kip1与恶性肿瘤发生、发展的关系。方法：查阅相关中外文献,分析Skp2和p27kip1的生物学特性和功能以及与常见恶性肿瘤的关系。结果：Skp2通过泛素蛋白酶体途径降解磷酸化的p27kip1,促使细胞由G1期进入S期,导致肿瘤的发生。结论：Skp2-p27kip1可能代表一种致癌通路,其与肿瘤的关系正受到越来越多的重视。     

p27~(kip1)在胃癌中的表达及与临床病理分期和预后的关系

目的 :探讨 p2 7kip1在胃癌中的表达状况及其预后价值。方法 :应用免疫组化技术 (S P法 )检测了 p2 7kip1在 6 7例胃癌中的表达。结果 :p2 7kip1在胃癌中的阳性表达率为 5 0 7% ,表达呈异质性。p2 7kip1的表达与胃癌的浸润深度 (P <0 0 5 )、淋巴结转移 (P <0 0 0 5 )、分化程度 (P <0 0 5 )及临床病理分期 (P <0 0 0 5 )显著相关 ,而与肿瘤大小、部位无关。结论 :p2 7kip1在胃癌中低表达反映了其恶性进展 ,是一个有价值的预后因子     

p27/kip1 expression in normal epithelium, benign and neoplastic breast lesions.

The development of cancer in the breast and in other sites is a complex process requiring a number of different genetic and epigenetic alterations. The accumulation of the genetic changes is thought to underlie the progression from precancerous lesions to carcinomas. The expression of p27/kip1 protein, a cyclin-dependent kinase inhibitor, was investigated by immunohistochemistry in normal epithelial specimens, benign alterations, and malignant lesions of the breast. The number of p27/kip1-positive cells ranged from none to more than 98% in the overall series. Wide ranges of p27/kip1-positive cells were consistently observed within each histological category, but the median value progressively decreased in typical hyperplasia and fibroadenoma, with an even more marked reduction in malignant lesions, compared with normal epithelium. Moreover, the percentage of cells expressing p27/kip1 in tumours was about three times lower in invasive than in in situ lesions and was inversely related to tumour size, but not to lymph node involvement. In conclusion, the degree to which p27 expression is altered in typical hyperplastic lesions and fibroadenomas indicates that the deregulation of p27 may occur very early on during breast cell transformation, but the usefulness of its determination to categorize subgroups of lesions at different risk of evolution remains somewhat doubtful.     

Expression of p27kip1 in breast cancer and its prognostic significance

p27kip1 is a member of the KIP/CIP family of cyclin-dependent kinase inhibitors and is a negative cell-cycle regulator that is thought to play a role in tumour suppression. Reduced levels of this protein have been observed in a number of human cancers. However, evidence is conflicting as to whether p27kip1 has a role to play in breast cancer, including predicting behaviour and prognosis. The present investigation aimed to provide a definitive study of 830 breast cancer cases with median patient follow-up of 104 months to determine the true prognostic significance, if any. Immunohistochemical analysis of tissue microarrays and three scoring methods were used to assess p27kip1 expression. Univariate analysis showed a significant relationship between reduced p27kip1 expression and increasing tumour grade, nuclear pleomorphism, mitosis, and decreasing tubule formation (all p<0.001). Significant associations between reduced p27, negative oestrogen receptor status, and ductal/no special type tumours were also observed. Survival analysis demonstrated that patients with tumours with high p27kip1 levels had an improved survival compared with those with cancers with low expression. On multivariate analysis, when compared with existing factors, p27kip1 was not, however, an independent prognostic factor. It is concluded that the inverse relationship between p27kip1 levels and histological grade and individual grade components suggests a role for p27kip1 in both cell proliferation and differentiation, but is not clinically useful.     

p27kip1和Skp2在损伤后大鼠坐骨神经中的表达变化

为了探讨损伤后周围神经p27kip1和S期激酶相关蛋白2(Skp2)的定位表达和变化,本实验将成年SD大鼠随机分为正常对照组、夹伤组和切断组,运用Western blot结合免疫组织化学及免疫荧光双标,在大鼠坐骨神经损伤时,对p27kip1和Skp2表达的影响进行了研究。结果表明:(1)坐骨神经夹伤后,p27kip1蛋白表达先逐渐下降,后又逐渐上升;坐骨神经切断后,远侧段p27kip1蛋白表达持续下降,而近侧段p27kip1蛋白表达在切断后6h明显下降,后又逐渐升高至正常水平,而Skp2表达变化与之相反;(2)免疫组织化学染色结果显示,坐骨神经切断后1w,远侧段从断端到末端,p27kip1阳性信号逐渐增加,而Skp2阳性信号逐渐减弱;(3)免疫荧光双标显示,正常和损伤坐骨神经的雪旺氏细胞中都有p27kip1和Skp2表达。以上结果提示:周围神经损伤后影响雪旺氏细胞中p27kip1和Skp2的表达变化,为进一步研究它们在周围神经损伤和修复中的作用机制奠定基础。     

p27(kip1) and Other Cell-Cycle Protein Expression in Normal and Neoplastic Endocrine Tissues

Endocrine tumors are often diagnostic challenges. Recent studies have suggested that proteins that regulate cell cycle may have diagnostic and prognostic utility in endocrine tumors. p27^{kip 1} (p27) is a cyclin-dependent kinase inhibitor that regulates the transition from the G1 to the S phase of the cell cycle. p27 and other cell-cycle proteins are becoming increasingly important in assessing the biologic behavior of endocrine neoplasms, classifying hyperplastic and neoplastic endocrine tissues, and in the progression of endocrine tumors. p27 appears to separate normal from neoplastic endocrine tissues and, in some cases, benign from malignant endocrine tumors. However, there is overlap in p27 expression among individual cases of benign and malignant tumors, and p27 has only limited prognostic utility in endocrine tumors compared to some epithelial tumors such as breast and prostate neoplasms. Thus, more effective molecular and cellular markers that can be used for diagnostic and prognostic purposes in endocrine pathology are needed.     

Prognostic implications of cyclin B1, p34cdc2, p27(Kip1) and p53 expression in gastric cancer

PURPOSE: Cell cycle progression is regulated by interactions of specific cyclins and cyclin dependent kinases (CDKs) at the G1-S and G2-M checkpoints and cell cycle deregulation plays a major role in carcinogenesis of human cancers. PATIENTS AND METHODS: To investigate the role of cell cycle regulators in the pathogenesis and progression of human gastric cancers, 23 cases of gastric carcinomas were examined for the expression of cyclin B1, p34cdc2, p27(Kip1) and p53 by immunohistochemical methods, and gene expression was correlated with various clinicopathologic findings. RESULTS: Out of 23 cases studied, cyclin B1 was diffusely expressed in 20 cases (87.0%), p34cdc2 in 14 cases (60.9%) and p53 in 12 cases (52.2%), whereas in normal gastric tissues, cyclin B1 and p34cdc2 were weakly expressed and p53 was not expressed. In contrast, p27(Kip1) was expressed in only 8.7% of gastric carcinomas compared with 78.3% of normal gastric tissues. There was correlation between the expression of cyclin B1 and expression of p34cdc2 (p=0.002), between the expression of cyclin B1 and loss of p27(Kip1) (p=0.025), and between the expression of p34cdc2 and loss of p27(Kip1) (p=0.065). In addition, expression of cyclin B1 was correlated with regional lymph node metastasis (p=0.032). CONCLUSION: Our results indicate that cyclin B1 and p34cdc2 are involved in the genesis or progression of gastric cancers. Furthermore, overexpression of cyclin B1 may play an important role in lymph node metastatic potential of gastric cancer. Thus, abnormal expression of cyclin B1 and CDKs, overexpression of p53 and loss of p27(Kip1) expression may play important roles in human gastric carcinogenesis.     

p27kip1基因对食管癌细胞DNA复制及蛋白质合成的影响

目的:研究p27kip1基因对人食管癌细胞EC-9706的DNA复制及蛋白质合成的影响。方法: 重组体腺病毒Ad-p27kip1转染EC-9706细胞, 采用细胞生长计数、 [³H]-TdR、[³H]-Leucine掺入法、流式细胞术,研究其对食管癌细胞DNA复制及蛋白合成的影响。结果: Ad-p27kip1组细胞生长明显受抑, [³H]-TdR、[³H]-Leucine掺入量均明显减少,与对照组比较P<0.01;食管癌细胞的增殖明显受抑制。结论: p27可有效抑制食管癌细胞的增殖活性,这与其抑制食管癌细胞DNA复制及蛋白质合成有关。     

反转录病毒载体介导的P27kip1促HepG2细胞凋亡简

 目的 研究反转录病毒介导的P27kip1基因过表达对HepG2细胞的影响。 方法 构建携带有人P27kip1基因的反转录病毒载体,经脂质体介导转染PA317包装细胞,G418筛选获得稳定产毒细胞株,病毒感染HepG2细胞,筛选出P27kip1阳性克隆,Western blot检测P27kip1在HepG2中的表达,并通过细胞形态学观察、MTT、FCW等方法,检测P27kip1对HepG2细胞的影响。结果 成功构建了含有人P27kip1基因的pLNCX-P27反转录病毒载体并导入包装细胞获得了稳定产毒细胞株,病毒感染HepG2后P27kip1基因可在细胞内高表达,过表达P27kip1基因的细胞生长速度受阻,较多细胞阻滞于G1期,且凋亡增多。结论 构建的pLNCX-P27载体能稳定高效地将P27kip1基因导入HepG2细胞,过表达P27kip1可抑制细胞生长,加速凋亡。     

Bottom-up cell proliferation with cyclin A and p27Kip1 expression in ulcerative colitis-associated dysplasia

To analyze the cell kinetics of ulcerative colitis (UC)-associated dysplasia, cyclin A, cyclin D1, cyclin E, cdk2, cdk4, p21(Waf1), and p27(Kip1) were immunohistochemically examined, in comparison with sporadic tubular adenomas. Immunohistochemical labeling indices for each marker in formalin-fixed paraffin-embedded tissue sections were assessed in a total of 23 low-grade dysplasias, 27 high-grade dysplasias, and 14 invasive adenocarcinomas associated with UC. For comparison, 21 sporadic tubular adenomas with low-grade dysplasia, 33 with high-grade dysplasia, and 21 invasive adenocarcinomas were also examined. In UC-associated dysplasias, cyclin A and p27(Kip1) were located in the lower parts of the crypts and p21(Waf1) in the upper regions. In tubular adenomas, cyclin A, cdk4, p27(Kip1), and p21(Waf1) were all expressed in the upper parts of the crypts. The expression levels of cyclin D1, cyclin E, and cdk2 were low. The cell proliferation zone in UC-associated dysplasia is located towards the bases of the crypts with the strong expression of cyclin A and p27(Kip1), in contrast to tubular adenomas, which have their cell proliferation zone in the upper parts of neoplastic crypts. It is considered that tumorigenesis with UC-associated dysplasia is of the bottom-up type, related to altered expression of cyclin A and p27(Kip1).     

乳腺浸润性导管癌中p57kip2、cyclin D1和cyclin E的表达及意义

目的探讨p57kip2、cyclin D1及cyclin E蛋白在乳腺癌发生、发展中作用.方法用免疫组化S-P法检测64例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)、15例乳腺导管原位癌(ductal carcinoma in situ,DCIS)和15例癌旁正常乳腺组织中p57kip2、cyclin D1和cyclin E蛋白的表达情况.结果p57kip2、cyclin D1和cyclin E蛋白在IDC的阳性率与在乳腺不同组织之间相比,cyclin D1、cyclin E蛋白在DCIS的阳性率与癌旁正常乳腺组织之间相比差异均有显著性(P≤0.05,P＜0.01).在IDC中,三者表达均与腋窝淋巴结转移有关(P≤0.05,P＜0.01),cyclin D1蛋白的表达与组织学分级有关(P＜0.01),cyclinE蛋白的表达与肿块大小有关(P＜0.01);p57kip2与cyclin D1之间、p57kip2与cyclin E之间的表达均呈负相关(P＜0.01)、cyclinD1与cyclin E之间的表达呈正相关(P＜0.01).结论p57kip2蛋白低表达、cyclin D1和cyclin E蛋白高表达可能是乳腺组织恶性转变以及乳腺癌发生淋巴结转移的重要生物学标志,cyclin D1和cyclin E蛋白异常表达是乳腺癌发生的早期事件.联合检测p57kip2、cyclin D1及cyclin E蛋白对预测乳腺癌淋巴结转移有重要意义.     

胃肠道类癌中p27kip1、PCNA表达及p16基因缺失

目的 :探讨 p2 7kip1 、PCNA及 p1 6与胃肠道类癌转移的关系。 方法 :采用免疫组化SABC法检测 2 5例胃肠道类癌组织中p2 7kip1 和PCNA蛋白表达 ,同时用PCR法检测 p1 6基因的缺失情况。 结果 :p2 7kip1 在胃肠道类癌阳性表达率为 64 % (1 6/ 2 5) ,PCNAⅠ～Ⅱ级和Ⅲ～Ⅳ级表达率分别为 56 %、44 %。 2种蛋白阳性表达率与分化程度无相关性 (P >0 0 5) ,与淋巴结转移相关 (P <0 0 5)。p2 7kip1 与PCNA表达负相关。p1 6基因纯合性缺失率为 48% (1 2 / 2 5) ,其缺失率与类癌分化程度和淋巴结转移无关。结论 :p2 7kip1 低表达、PCNA高表达与胃肠道类癌转移有关 ,胃肠道 ;类癌的发生与p1 6基因缺失有关 ,但可能为早期分子事件。     

p57kip2、cyclin D1在食管癌中的表达及意义

目的研究p57kip2在食管癌中的表达及意义,探讨其与cyclin D1在食管癌中表达的相关性。方法采用免疫组织化学SP法检测50例食管癌组织及15例正常食管上皮组织中p57kip2、cyclin D1的表达情况;应用流式细胞术对这些组织的DNA含量和细胞周期分布进行分析。结果免疫组化:p57kip2蛋白在食管癌组织中阳性表达率(34.0%)低于正常组织(80%)(P<0.01),与食管癌组织分化程度、浸润深度和淋巴结转移情况有关(P<0.05);cyclin D1蛋白在食管癌组织中的阳性表达率(64.0%)高于正常组织(13.33%)(P<0.01),与浸润深度和淋巴结转移情况有关(P<0.05),与食管癌组织分化程度无关(P>0.05)。p57kip2和cyclin D1之间表达负相关(r=-0.429,P<0.01)。流式细胞术:与正常组织相比,癌组织中DNA含量增高,异倍体细胞增加;G0/G1期细胞减少,而S期和G2/M期细胞增多,增殖指数(PI)高于正常组织。结论p57kip2蛋白低表达可能与食管癌的发生发展有关;p57kip2与cyclin D1联合检测可作为评估食管癌恶性程度指标。     

结直肠癌中cyclin D1和p27蛋白的表达及其意义

目的　研究cyclinD1和p2 7蛋白在结直肠癌发生、发展中的作用及其与结直肠癌临床病理特征关系。 方法　收集5 8例手术切除的结直肠癌标本 ,同时取距癌灶 >5cm的正常组织 ,应用免疫组化S P法检测癌组织及正常组织中cyclinD1和p2 7蛋白的表达。结果　cyclinD1蛋白在结直肠癌的表达阳性率为 5 5 17%,正常组织无表达 (P <0 0 1) ;cyclinD1蛋白的表达阳性率在 6 0岁以上年龄组高于 6 0岁以下年龄组 (P <0 0 5 ) ;cyclinD1蛋白的表达与肿瘤组织分化程度负相关 (P <0 0 1)。p2 7蛋白在结直肠癌的表达阳性率为 5 5 17%,在结直肠正常组织的表达阳性率为 96 5 5 %(P <0 0 1) ;p2 7蛋白的表达与肿瘤组织分化程度负相关 (P <0 0 1)。cyclinD1和p2 7蛋白在结直肠癌的表达呈正相关 (r =0 5 82P <0 0 1)。 结论　cyclinD1蛋白过表达与 p2 7蛋白失活可加速细胞周期转化 ,促进结直肠癌的发生 ,cyclinD1和 p2 7蛋白的检测可作为评价结直肠癌恶性程度和判断预后的重要指标。