p53基因CD72 Arg／Pro多态性与肿瘤易感性研究进展

p53基因是迄今发现的与人类恶性肿瘤相关性最强的基因。过去对p53基因的丢失、突变、蛋白的表达做了大量研究。近年来研究发现，p53基因CD72 Arg／Pro多态性与多种肿瘤的发病有关联。本文拟对p53基因该多态位点与肿瘤的研究进展做一综述。     

p53基因CD72 Arg/Pro多态性与肿瘤易感性研究进展

p53基因是迄今发现的与人类恶性肿瘤相关性最强的基因。过去对p53基因的丢失、突变、蛋白的表达做了大量研究。近年来研究发现,p53基因CD72 Arg/Pro多态性与多种肿瘤的发病有关联。本文拟对p53基因该多态位点与肿瘤的研究进展做一综述。     

p27Kip1与肿瘤

真核生物的细胞周期进程是由一系列调控因子有序的聚合和激活来调节控制的,其正常与否和细胞以及个体的生长、分化、衰老和癌变密切相关。参与细胞周期调控的主要分子有：细胞周期蛋白（ｃｙｃｌｉｎ）,细胞周期蛋白依赖性激酶（ｃｙｃｌｉｎｄｅｐｅｎｄｅｎｔｋｉｎａ...     

乳腺癌组织P21WAF1基因多态性与蛋白表达的关系

目的 :探讨乳腺癌组织p2 1WAF1DNA多态性与蛋白表达的关系。方法 :分别采用聚合酶链反应单链构象多态性技术 (PCR -SSCP)和免疫组化S -P法检测 10 0例乳腺癌石蜡包埋组织和 4 0例乳腺良性病变组织p2 1WAF1DNA多态性和蛋白表达。结果 :18% (18/ 10 0 )的乳腺癌组织和 5 % (2 / 4 0 )对照组组织分别出现两种p2 1WAF1DNA多态性 ,前者明显高于后者 ,组间有显著差异 (χ2 =3 94 ,P <0 0 5 ) ;5 0 % (5 0 / 10 0 )的乳腺癌组织和 12 5 % (5 / 4 0 )对照组组织表达p2 1WAF1蛋白 ,前者明显高于后者 ,组间有显著差异 (χ2 =16 84 ,P <0 0 1) ;10 0 % (18/ 18例 )的具有p2 1WAF1DNA多态性的乳腺癌组织p2 1WAF1蛋白表达阳性 ,39% (32 / 82 )的无p2 1WAF1DNA多态性乳腺癌组织蛋白表达阳性 ,p2 1WAF1DNA多态性组明显高于无多态性组 ,组间有显著差异 (χ2 =2 1 95 ,P <0 0 1) ;p2 1WAF1DNA多态性与p2 1WAF1蛋白表达呈正相关 (r =0 5 76 ,P <0 0 1)。结论 :乳腺癌组织p2 1WAF1DNA多态性可能产生不同的转录本并生成相应的蛋白质分子。     

IL-27 p28基因多态性与中国汉族人群类风湿性关节炎的相关性研究

目的:探讨中国汉族人群IL-27p28基因多态性与类风湿性关节炎易感性的关系。方法:采用聚合酶链式反应PCR技术检测103例类风湿性关节炎患者和104例健康对照者IL-27p28启动子区-964A/G,外显子区2905T/G、g.4730T/C的基因型。计算并对比分析出两组人群的基因型频率和等位基因频率及其分布情况。结果:病例组和对照组的基因型分布均符合Hardy-weinberg平衡定律(P>0.05)。所检测三个位点的基因型频率及等位基因频率在病例组和对照组间的差异均无统计学意义(P>0.05)。结论:IL-27p28基因启动子区和外显子区单核苷酸多态-964A/G和2905T/G、g.4730T/C均未发现与中国汉族人群类风湿性关节炎的易感性有显著关联。     

p27与肿瘤的研究进展

肿瘤的发生、发展和恶变与细胞周期失控密切相关。细胞周期的顺利进行和完成依赖于一系列正负调节因子的相互作用 ,主要有细胞周期素 (cyclins)、细胞周期素依赖激酶(cyclin -dependentkinases,CDKs)和细胞周期素依赖激酶抑制蛋白 (cyclin -dependentkinaseinhibitors ,CDKIs)。CDKIs是近几年来分离得到的一类重要的细胞周期调控蛋白 ,参与细胞G1期进入S期的负调控 ,可防止细胞过度增殖和恶变。p2 7是新近发现的CDKIs家族成员之一。1 p2 7基因及其蛋白1994年 ,Polyak等[1] 在转化生长因子 - β(TGF - β)和经细胞接触处理的生长抑…     

p53基因多态性与卵巢癌

在抑癌基因中 ,p5 3与肿瘤的关系较早受到人们的重视 ,而且是迄今研究的最为广泛、最为系统的抗癌基因之一。本文论述 p5 3基因的结构与蛋白的功能 ,以及 p5 3基因的几个多态性位点。就近年来 p5 3基因的多态性与散发性和遗传性卵巢癌的相关研究做一简要综述 ,并对以后 p5 3基因多态性的研究方向提出一些建议。     

p53基因第72位密码子多态性与宫颈癌相关性

目的　探讨 p5 3基因第 72位密码子多态性与新疆汉族人群宫颈癌发生的关系。 方法　采用限制性酶切片段多态性分析 (RFLP)技术检测 72例宫颈癌及正常宫颈石蜡包埋组织中p5 3基因多态性的分布 ,分析两者之间的相关性。结果　p5 3基因 3种基因型Arg/Arg、Pro/Pro、Pro/Arg在宫颈癌中所占比例分别是 2 1 0 % ,39 5 % ,39 5 % ,对照组为 38 2 % ,14 7% ,4 7 1% ,两组总构成比差异有显著性 (χ2 =6 0 1,P <0 0 5 ) ,Pro/Pro在宫颈癌中所占比例高于对照组 ,没有发现Arg/Arg在宫颈癌中所占比例高于对照组 ,在HPV16、18阳性宫颈癌中所占比例分别是 2 2 2 % (4 /18)、5 0 0 % (9/18)、2 7 8% (5 /18) ,Pro/Pro所占比例明显高于其它两型。结论　p5 3Pro/Pro基因型可能是新疆汉族女性宫颈癌主要遗传易感因素。     

肝细胞癌p53基因与p21WAF1／CIP1基因的相关性分析

近年来，癌基因、抑癌基因在肿瘤发生发展中的作用日益受到人们的关注，不少学者进行了ｐ５３基因与肝细胞肝癌（ＨＣＣ）发生的相关性研究。有作者报道，野生型ｐ５３基因抑制细胞增殖的功能是通过ｐ２１ＷＡＦ１／ＣＩＰ１基因介导的〔１〕。本文检测７２例ＨＣＣ组织中...     

胃癌组织中p21、p27、p53和Rb的表达及临床意义

目的 探讨p21、p27、p53和Rb蛋白表达在胃癌发生、发展中的作用.方法 应用免疫组化EnVision法检测111例胃癌,38例不典型增生、47例肠上皮化生、25例慢性萎缩性胃炎和53例正常胃黏膜组织中p21、p27、p53和Rb蛋白的表达.结果 p21和p27蛋白表达水平在不典型增生组织最高,其次是胃癌组织,与正常胃黏膜组织相比差异均有显著性(P<0.001).在胃癌组织中p21、p27、p53和Rb蛋白表达均高于正常胃黏膜组织(P均＜0.01).p21、p27蛋白表达与胃癌的类型和分化相关(P均＜0.01),p53表达水平与患者的年龄、性别、胃癌的类型和患者的生存率相关.女性患者Rb蛋白表达明显高于男性,差异有显著性(P<0.05).p21、p27、p53和Rb蛋白表达水平之间均呈正相关.结论 p21、p27、p53和Rb蛋白表达可以作为胃癌的辅助诊断指标,四种蛋白在判断胃癌的生物学行为上具有协同作用.     

Overexpression of p21, cyclin E and decreased expression of p27 in DMBA (7, 12-dimethylbenzanthracene)-induced rat ovarian carcinogenesis

Ovarian cancer is a common gynecological malignancy and a leading cause of death in women. Inactivation of the tumor suppressor gene and deregulation of cyclin E are frequent in human ovarian cancer. The objective of this study was to investigate the expressions and roles of cyclin E, p21 and p27 in 7, 12-dimethylbenzanthracene (DMBA)-induced ovarian tumors in rats. The expressions of cyclin E, p21 and p27 were evaluated by immunohistochemistry and western blot analysis. The expressions of cyclin E and p21 in ovarian tumors was higher than that in normal ovarian surface epithelium. In contrast, the expression of p27 in ovarian tumors was lower than that in normal ovarian surface epithelium. But there were no differences among the cancer types. Positive correlation was present between cyclin E and p21. p27 was negatively correlated with cyclin E and p21. These results suggest that the increased expression of cyclin E and p21, and the decreased expression of p27, occur in DMBA-induced rat ovarian carcinogenesis and result in tumor progression.     

细胞周期素依赖性激酶2及p27Kipl与血管瘤

目的:进一步探讨细胞周期素依赖性激酶2(CDK2)及p27Kipl.在血管瘤发生、发展及退化过程中的作用机制.方法:采用免疫组织化学SP法检测49例皮肤毛细血管瘤增生期、退化期及正常皮肤组织中CDK2和p27Kipl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CDK2和p27Kipl表达的平均光密度和阳性面积率进行图像分析.结果:增生期组CDK2的表达明显高于退化期组和正常皮肤组织组;增生期血管瘤内皮细胞p27Kipl的表达显著低于退化期血管瘤内皮细胞.结论:p27Kipl能抑制血管瘤内皮细胞的增殖,在血管瘤的退化过程中起了重要作用;而CDK2能促进血管瘤内皮细胞增殖,存血管瘤的增生过程巾起了重要作用.     

Combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma

AIMS: In order to estimate the prognostic values of p27(Kip1), p21(Waf1/Cip1), and p53, alone and in combination, we investigated immunohistochemically the expression of p27(Kip1), p21(Waf1/Cip1), and p53 proteins in gastric carcinomas. METHODS AND RESULTS: The expression of p27(Kip1), p21(Waf1/Cip1), and p53 was immunohistochemically examined in 140 gastric carcinomas. Positive expression of p27(Kip1) and p21(Waf1/Cip1) correlated significantly with a favourable prognosis (P < 0.05), whereas, positive expression of p53 tended to correlate with poor prognosis. Multivariate survival analysis revealed that TNM stage of tumour (P < 0.001), lymph node state (P=0.005), and p27(Kip1) expression (P=0.006) were independent prognostic factors. A striking stratification of mortality rate was found when patients were divided into four groups according to the expression of p21(Waf1/Cip1) and p27(Kip1). The mortality rate was higher in patients with both p21(Waf1/Cip1)- and p27(Kip1)-negative gastric carcinoma than in patients with one or both positive carcinomas (P < 0.01). In addition, if the four p21(Waf1/Cip1)/p27(Kip1) groups were compared based on p53 status, p53+ cases tended to have a higher mortality rate than p53- cases. CONCLUSION: Our results suggest that low expression of both p27(Kip1) and p21(Waf1/Cip1), could be useful as markers of poorer prognosis, and the combined examination of p27(Kip1), p21(Waf1/Cip1) and p53 expression allows reliable estimation of prognosis for patients with gastric carcinoma.     

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.     

PTEN及p27Kip1在子宫内膜癌中的研究进展

肿瘤抑制基因PTEN被称为子宫内膜的看家基因,许多学者提出PTEN基因在子宫内膜癌发生发展中起重要作用。另一个肿瘤抑制基因p27在子宫内膜癌的预后中具有重要的作用。现就PTEN 、p27基因在子宫内膜癌中的表达及其与子宫内膜癌发生、发展的关系以及在治疗和预后方面的研究进展进行综述。     

Down-regulation of p27Kip1 expression is correlated with increased cell proliferation but not expression of p21waf1 and p53, and human papillomavirus infection in benign and malignant tumours of sinonasal regions

AIMS: Although p27Kip1(p27) is a cyclin-dependent kinase inhibitor and a contribution to tumorigenesis has been hypothesized, the possible role in tumours arising in the nasal and paranasal sinus regions is still unknown. METHODS AND RESULTS: Seventy-six sinonasal tumours, including 28 inverted papillomas (IPs) and 48 squamous cell carcinomas (SCCs), were immunohistochemically investigated, along with 46 exophytic papillomas (EPs) of upper respiratory tract and 34 samples of normal paranasal sinus epithelium. The results were also compared with expression of p21WAF1 (p21) and p53, cell proliferation assessed in terms of Ki67 labelling indices (LIs), and human papillomavirus (HPV) infection. The average p27 scores decreased from normal through to malignant lesions, while Ki67 LI scores showed a stepwise increase, the inverse correlation between scores for all categories being significant (r = - 0.639, P < 0. 0001). In the SCCs, p27 expression was significantly higher in keratinizing than nonkeratinizing type tumours (P < 0.05), while there was no association with p21 and p53 expression. Although HPV DNAs for type 16 and 18 were detected in two (7.4%) of 27 EPs, six (35.8%) of 28 IPs, and nine (28.1%) of 32 SCCs, no relation with p27 scores was evident. CONCLUSION: Loss of p27 expression correlates with increased cell proliferation in sinonasal tumours. Moreover, the expression appears to be associated with keratinization in SCCs of the paranasal sinus. These findings indicate that p27 expression may be a useful marker for the dysregulation of cell kinetics in these tumours.     

p27基因和蛋白表达的调控及其在肿瘤发生机制中的作用

p27-kip1基因编码的P27蛋白作为细胞周期蛋白依赖性激酶抑制剂,在细胞周期进程中起重要的负调节作用,同时作为一个新的肿瘤抑制基因,与肿瘤的发生、发展及预后密切相关,近年来调节P27机制的新发现为肿瘤治疗开辟了新的道路。     

Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status

p21Waf1 (p21), p27Kip1 (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, studies on these cell cycle regulators in ductal carcinoma in situ (DCIS) have been extremely limited. Therefore, we studied the immunohistochemical expression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared the findings with the clinicopathologic parameters (age, tumor size, gross type, histologic type, histologic grade, necrosis and mitotic index), p53 and estrogen receptor (ER) status. A significant correlation was found between positive p21 immunoreactivity (67.3% of the cases) and well-differentiated histologic grade, non-comedo type, ER-positive and p53-negative (p53-) status. DCIS with p21+/p53- is likely to be the non-comedo type. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) correlated with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cyclin D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.