胃癌组织Skp2表达的意义及其与P27、PTEN表达的关系

背景与目的:S期激酶相关蛋白2(S-phaseKinase-associatedProtein2,Skp2)促进泛素介导的细胞周期素依赖激酶抑制剂P27蛋白降解,是细胞G1-S期转化所必需。研究发现Skp2过表达参与细胞转化和肿瘤的形成。本研究旨在探讨人胃癌Skp2表达的意义及Skp2与P27和PTEN表达的关系。方法:采用免疫组化法检测胃癌组织及配对癌旁胃粘膜138例、配对淋巴结转移癌组织102例、非典型增生30例、肠上皮化生30例、慢性浅表性胃炎10例和正常胃粘膜5例Skp2表达及138例胃癌P27和PTEN的表达。结果:Skp2的标记率(%)在肠化(12.68±0.86)及癌旁胃粘膜(19.32±1.22)均明显高于慢性浅表性胃炎(0.53±0.13)及正常胃粘膜(0.47±0.19)(P<0.001),后两者无显著性差异(P﹥0.05);非典型增生(16.74±0.82)明显高于肠化(P<0.001);原发胃癌(31.34±2.17)明显高于非典型增生及癌旁胃粘膜(P<0.001);淋巴结转移胃癌组织(39.76±2.00)明显高于原发胃癌(P=0.037)。胃癌Skp2标记率与分化程度(rs=0.315,P=0.000)、脉管内瘤栓(rs=0.303,P=0.000)及淋巴结转移(rs=0.254,P=0.000)呈正相关。胃癌Skp2表达与靶蛋白P27表达(rs=-0.451,P=0.000)和肿瘤抑制蛋白PTEN(rs=-0.480,P=0.000)表达呈负相关;胃癌PTEN表达与P27表达呈正相关(rs=0.642,P=0.000)。结论:胃癌Skp2蛋白过表达与P27蛋白降解及PTEN蛋白低表达有关,提示Skp2蛋白过表达可能是胃癌发生和发展的一个重要原因。     

Skp2和P27kip1在前列腺癌组织中的表达与临床病理特征的相关性研究

背景及目的:F-box蛋白Skp2参与细胞周期抑制蛋白P27kip1泛素化降解,研究发现Skp2在乳腺癌、胃癌、前列腺癌等多种恶性肿瘤中表达增加.本研究旨在探讨Skp2和P27kip1在前列腺癌组织中的表达及与前列腺癌各项临床病理特征的关系,并探讨两者的相关性.方法:用免疫组化EnVisionTM方法检测Skp2和P27 kip1蛋白在41例前列腺癌和20例良性前列腺增生组织中的表达情况.结果:在前列腺癌中的Skp2蛋白阳性率[(8.52±2.40)%]显著高于良性前列腺增生[(0.21±0.15)%](P＜0.001).Skp2蛋白表达与前列腺癌术前血清前列腺特异性抗原(PSA)水平(r=0.360,P=0.021)、局部浸润(r=0.570,P＜0.001)、肿瘤分期(r=0.531,P＜0.001)、病理分级(r=0.514,P=0.001)呈正相关.在前列腺癌中的P27kip1蛋白阳性率[(70.71±4.25)%]显著低于良性前列腺增生[(97.21±2.10)%](P＜0.001).P27kip1蛋白表达与前列腺癌术前PSA水平(r=-0.399,P=0.010)、局部浸润(r=-0.329,P=0.036)、肿瘤分期(r=-0.453,P=0.003)、病理分级(r=-0.290,P=0.046)呈负相关.前列腺癌中P27kip1蛋白与Skp2表达呈负相关(r=-0.572,P＜0.001).结论:前列腺癌中Skp2蛋白表达与靶蛋白P27 kip1蛋白降解有关,提示Skp2蛋白可能与前列腺癌的发生发展有关.     

食管癌组织中Skp2和p27的表达及临床意义

目的 探讨 S期激酶相关蛋白2（Skp2）和p27在食管癌组织中的表达及其临床意义。方法 免疫组化法检测82例食管癌和10例癌旁组织中Skp2、p27的表达;分析Skp2、p27蛋白表达率与临床病理特征的关系;采用Spearman秩相关法分析两者的关系。结果Skp2在食管癌和癌旁组织中的阳性表达率分别为67.07%（55/82）和20.00%（2/10）,差异有统计学意义（P＜0.01）。p27在食管癌和癌旁组织中的阳性表达率分别35.37%（29/82）和90.00%（9/10）,差异具有统计学意义（P＜0.01）。Skp2蛋白表达与性别、年龄、肿瘤部位均无关（P＞0.05）,与分化程度、肿瘤侵犯深度、淋巴结转移和TNM分期有关（P＜0.05）。p27蛋白表达与性别、年龄、肿瘤部位、肿瘤侵犯深度、TNM分期无关,与分化程度、淋巴结转移有关（P＜0.05）。Skp2、p27蛋白表达呈负相关（r=-0.750,P＜0.001）。结论Skp2和p27参与正常食管组织向食管癌的演变,可能与食管癌的发生和发展有关。     

非小细胞肺癌组织中Skp2的表达及其与p27kip1和Ki-67蛋白表达的关系

目的:探讨Skp2的表达在非小细胞肺癌(nonsmallcelllungcancer,NSCLC)发生发展中的作用,及其与p27kip1和Ki67蛋白表达的关系。方法:应用免疫组化SP法检测Skp2、p27kip1和Ki67三种蛋白在60例NSCLC和20例正常支气管黏膜上皮组织中的表达。结果:NSCLC组织中Skp2蛋白表达的阳性率为48.33%(29/60),显著高于正常支气管黏膜上皮组织中的表达,P=0.000。Skp2的表达与肿瘤的组织学类型、肿瘤细胞的分化程度、TNM分期、淋巴结转移和患者吸烟与否显著相关,P值分别为0.038、0.005、0.019、0.010和0.002,但与患者的年龄及性别无关,P值分别为0.833和0.281。NSCLC组织中Skp2表达与p27kip1表达呈显著负相关,P=0.001;而与Ki67表达呈显著正相关,P=0.027。结论:Skp2在NSCLC组织中表达是上调的,可能是通过作用于细胞周期调控蛋白p27kip1,加速了对p27kip1泛素化依赖的蛋白降解,使其表达及代谢发生异常,导致细胞周期失控并促进细胞异常增殖,从而参与了NSCLC的发生和发展。     

Correlation of Skp2 with carcinogenesis, invasion, metastasis, and prognosis in colorectal tumors

In colorectal tumors, S-phase kinase-associated protein 2 (Skp2) still has numerous important questions unanswered: its expression in adenomas, its correlation with key clinicopathological indices, its association with patient prognosis, its variation in lymph node metastases, and its association with many cell-cycle regulators. To answer these questions in colorectal tumors, Skp2, cyclin A, cyclin B1, cyclin E, CDK2, and Ki67 were immunohistochemically stained in 12 normal mucosa, 36 adenomas, 11 carcinomas in adenomas, 102 primary carcinomas, and 12 paired lymph node metastases; and Skp2 was examined by Western blot in 8 pairs of normal mucosa and carcinomas. Situated in nuclei, Skp2 expression significantly increased from normal mucosa through adenoma to primary carcinoma (p<0.0001), from mild through moderate to severe dysplasia in adenomas (p=0.038), from peripheral adenoma to paired central carcinoma (p=0.0033), and from primary carcinoma to lymph node metastasis (p=0.015), and these increases were confirmed by Western blot. Expression, however, relatively declined significantly in the primary carcinomas showing deep invasion (p=0.0113), lymph nodal metastases (p=0.0268), and poor prognosis for all (p=0.0104) or stage III patients (p=0.0119). High Skp2 was also significantly linked with elevated cyclin A, cyclin B1, cyclin E, CDK2 (in primary carcinomas only), and Ki67 in both adenomas and primary carcinomas. Thus, overexpression of Skp2 is associated with colorectal carcinogenesis and late metastasis to lymph nodes, whereas relative reduction of Skp2 is correlated with local invasion of primary carcinoma.     

Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival.

The F-box protein Skp2 (Fbl1) is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis in both in vitro and in vivo models. In this study, we investigated its role in human prostate cancer progression. Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 622 radical prostatectomy specimens, 74 prostatic intraepithelial neoplasm specimens, as well as in 4 normal prostate organ donors assembled into tissue microarrays. We found that both luminal and basal epithelial cells in normal prostate had very low Skp2 levels, but Skp2 levels and labeling frequency increased dramatically in both premalignant lesions of prostatic intraepithelial neoplasm (P = 0.0252) and in prostate cancer (P = 0.0037). The Skp2 labeling frequency in cancer was positively correlated with preoperative serum prostate-specific antigen level (P = 0.0499) and Gleason score (P = 0.0002), whereas the Skp2 index was positively correlated with extraprostatic extension (P = 0.0454), clinical stage (P = 0.0170), as well as Gleason score (P = 0.0002). Kaplan-Meier analysis revealed that a higher Skp2 labeling index (>10) was a significant predictor of shorter biochemical recurrence-free survival time after radical prostatectomy (P < 0.0363, log-rank test). An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in prostate cancer (P = 0.0003) and with its putative negative regulator, the PTEN tumor suppressor protein (P = 0.0444). These data suggest that induction of Skp2 may be causally linked with decreased levels of p27 in prostate cancer and implicate PTEN in the regulation of Skp2 expression in vivo, as previous tissue culture experiments have suggested.     

胃癌中Cks1、P27Kip1、Skp2蛋白表达相关性及其意义

目的:探讨Cks1在胃癌发生及Skp2调节P27Kip1降解过程中的作用。方法:应用流式细胞术检测正常胃黏膜、胃不典型增生组织及胃癌组织中Cks1、P27Kip1、Skp2蛋白的表达。结果:由正常胃黏膜、胃不典型增生组织到胃癌中Cks1、Skp2的表达均呈上升趋势(P<0.05),P27Kip1表达则呈下降趋势(P<0.05)。胃癌中Cks1、Skp2表达均与P27Kip1表达呈负相关(r=-0.649,P<0.05;r=-0.732,P<0.05);而Cks1蛋白表达与Skp2蛋白无相关性(P>0.05)。胃癌中Cks1表达与肿瘤分化程度相关(P<0.05),而与肿瘤浸润深度、淋巴结转移及临床分期不相关(P>0.05)。结论:Cks1可能参与胃癌的发生;胃癌中Cks1可能参与Skp2调节P27Kip1泛素化的降解过程。     

Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma: modulation of malignant phenotype by Skp2 overexpression,possibly via p27 proteolysis

Reduced expression level of p27, a cyclin-dependent kinase inhibitor, is associated with high aggressiveness and poor prognosis of various malignant tumors, including gastric carcinoma. S-phase kinase-associated protein 2 (Skp2), a member of the F-box family of substrate-recognition subunits of Skp1-Cullin-F-box ubiquitin-protein ligase complexes, is necessary for p27 ubiquitination and degradation. In the present study, we examined the clinical and biological significance of Skp2 expression in human gastric carcinoma and the relationship between the expression of Skp2 and p27. Northern blot analysis showed that Skp2 mRNA was overexpressed in carcinoma tissues (P < 0.05), and the high Skp2 expression group showed significantly poorer prognosis in 98 patients with gastric carcinoma (P < 0.05). Immunohistochemical analysis showed that Skp2 protein was expressed predominantly in carcinoma cells. We also found an inverse correlation between the expression of Skp2 mRNA and p27 protein in vivo (P < 0.01). To analyze the biological behavior of Skp2, we established stably Skp2-transfected gastric carcinoma cell lines. Western blot analysis showed that Skp2-transfected cells expressed lower levels of p27 protein than the control cells. Skp2-transfected cells showed significantly higher levels of growth rate (P < 0.05), percentage of bromodeoxyuridine-positive cells after serum starvation (P < 0.01), resistance to apoptosis induction by actinomycin D treatment (P < 0.05), and invasion potential (P < 0.01) than the control cells. These findings indicate that Skp2 expression can modulate the malignant phenotype of gastric carcinoma, possibly via p27 proteolysis. Skp2 can play an important role in gastric carcinoma progression and would be a novel target for the treatment of gastric carcinoma as well as a strong prognostic marker.     

COX-2 correlates with F-box protein, Skp2 expression and prognosis in human gastric carcinoma

The expression of cyclooxygenase (COX)-2 is induced by growth factors, tumor promoters and cytokines, and is correlated with carcinogenesis, tumor progression and inhibition of apoptosis. To clarify the pathological significance of COX-2, we examined the effect of a selective COX-2 inhibitor, NS398, on two human gastric carcinoma cell lines, MKN-45 and KATO-III, and the expression of Skp2, P27/Kip1 and COX-2 protein in human gastric carcinomas. NS398 inhibited cell growth in a time- and dose-dependent manner and exerted cell cycle arrest in the G0/G1 phase without induction of apoptosis in MKN-45, but had no effect in KATO-III. In MKN-45, NS398 induced up-regulation of P27/Kip1 and down-regulation of COX-2, cyclin D1 and Skp2. Immunohistochemistry using 63 surgically resected gastric carcinomas disclosed that COX-2 expression was correlated with Skp2 expression and that P27/Kip1 expression was inversely correlated with COX-2 and Skp2 expression. High levels of COX-2 or Skp2 were significantly correlated with poor survival (P=0.02 and P=0.004). Our results suggested that: a) NS398 induced inhibition of cell proliferation through cell cycle arrest and suppressed the expression of Skp2 in COX-2-expressing gastric carcinoma cells, and b) COX-2 contributes to the expression of Skp2 and poor survival in human gastric carcinomas.     

Clinical significance of Skp2 expression, alone and combined with Jab1 and p27 in epithelial ovarian tumors

We have previously demonstrated the inverse correlation of Jab1 and p27 proteins, as well as prognostic significance in epithelial ovarian carcinomas. In order to investigate Skp2 protein and its correlation with Jab1, p27, and clinical outcome, we evaluated Skp2 expression in a group of epithelial ovarian tumors. Immunohistochemical analysis was performed on 80 cases of ovarian tumors (33 benign and 47 malignant), and 26 of the 80 cases were evaluated by Western blot analysis. Immunofluorescence was carried out in the human ovarian adenocarcinoma cell line OVCAR-3. Skp2 expression was detected in 53.2% of malignant tumors and 18.2% of benign tumors. The positive ratio of Skp2 expression was increased from benign to malignant ovarian tumors (p=0.002). A negative correlation between Skp2 and p27 was found in benign and malignant ovarian tumors (p=0.006 and p<0.0001, respectively). Skp2 expression was significantly associated with high tumor grade (p=0.001), lymph node metastasis (p=0.01), and residual disease (p=0.012). Kaplan-Meier survival analysis showed that Skp2 expression was significantly associated with poor prognosis (p=0.013), and patients with Skp2(+)/Jab1(+)p27(-) expression had the worst prognosis among all phenotypes of Skp2/Jab1/p27 expression (p=0.0007). Our results suggest that Skp2 expression was significantly associated with malignancy, and the Skp2 protein level may be a valuable prognostic factor for epithelial ovarian carcinomas. Furthermore, the combined evaluation of Skp2/Jab1/p27 proteins provides important prognostic information on patients with epithelial ovarian carcinoma.     

Skp2与p27在大肠癌中的表达及临床病理关系的研究

Objective: The aim of this study was to study the expression and the clinical pathological relationship of p27 and Skp2 in the tissues of colorectal cancer,discuss the correlation between them.Methods: To determine the expressions of p27and Skp2 among 30 cases of colorectal cancer tissue specimen and 18 cases of normal colorectal tissue samples with immunohistochemistry SP method.Results: The average positive rate of p27 among the normal colorectal tissue samples was55.2%,which was obviously higher than that of colorectal cancer tissue samples(27.5%,P<0.05).The correlation between the expression of p27 and the degree of differentiation of colorectal cancer; Dukes stage and lymph node metastasis were distinctly negative(P<0.05).The average positive rate of Skp2 among the colorectal cancer tissue specimens was 9.5%,which was obviously higher than that of normal colorectal tissue samples(1.8%,P<0.05).There was an obviously negative correlation between the expression of Skp2 and the degree of differentiation of colorectal cancer(P<0.05),and the expression of Skp2 had no significant correlation with patients' age,sex,Dukes stage and lymph node metastasis(P>0.05).There was an negative correlation between the expression of p27 and Skp2(r=-0.806,P<0.01).Conclusion: The expression of Skp2 in the colorectal cancer tissues is correlative with the degradation of p27;Skp2,the oncogene of colorectal cancer,is involved in colorectal carcinogenesis,which may be the new target for the treatment of colorectal cancer.     

S期激酶相关蛋白2与间隙连接蛋白43在子宫颈癌中的表达及其意义

目的 探讨S期激酶相关蛋白2(Skp2)和间隙连接蛋白43(Cx43)在子宫颈癌中的表达及其临床意义.方法 采用免疫组织化学SP法检测48例子宫颈癌、84例子宫颈上皮内瘤变(CIN)(CINⅠ～Ⅱ级45例、Ⅲ级39例)、28例慢性子宫颈炎患者Skp2和Cx43的表达.结果 子宫颈癌组织中Skp2表达水平高于CINⅠ～Ⅱ级组及慢性子宫颈炎组(P<0.05),而Cx43蛋白表达水平低于CINⅢ级组、CINⅠ～Ⅱ级组及慢性子宫颈炎组(P<0.05);Skp2的阳性表达与子宫颈癌分化程度、淋巴结转移有关(P<0.05);Cx43的表达缺失与淋巴结转移有关(P<0.05);子宫颈癌组织中Skp2和Cx43的表达呈负相关.结论 Skp2与Cx43的表达程度与子宫颈癌的发生、发展密切相关,且两者之间可能存在相互作用.     

大肠癌组织PTEN和Skp2蛋白表达与预后相关性的探讨

目的:观察大肠癌组织中PTEN缺失和Skp2表达情况,并观察两者与大肠癌临床病理特征和预后的关系,探讨其在大肠癌预后的价值.方法:采用SP方法检测大肠癌组(61例)和对照组(20例)中PTEN和Skp2蛋白的表达,分析其表达与患者临床病理特征和5年生存率的关系,并观察两者之间的相关性.结果:大肠癌组PTEN表达率(72.13％)明显低于对照组(100.00％);大肠癌组Skp2表达率(52.46％)明显高于对照组;PTEN缺失和Skp2的表达均与组织分化程度、淋巴结转移和临床分期呈正相关.PTEN阴性组的5年生存率(31.86％)低于阳性组(83.97％),Skp2阳性组的5年生存率(58.33％)低于阴性组(82.76％).PTEN和Skp2的表达呈负相关,r=-0.445,P=0.001.结论:PTEN缺失和Skp2表达可能与大肠癌发生、转移和预后有关,联合检测PTEN和Skp2蛋白可作为预测大肠癌发生转移和预后的指标.     

Skp2与Cx43蛋白在子宫颈癌中的表达及其意义

 目的　探讨Skp2和Cx43在子宫颈癌中的表达、相关性及临床意义。方法　采用免疫组织化学方法检测48例子宫颈癌、84例子宫颈上皮内瘤变（其中CINⅠ～Ⅱ45例、CINⅢ39例）、及28例慢性子宫颈炎组中Skp2和Cx43的表达。结果　子宫颈癌组织中Skp2表达水平高于CINⅠ～Ⅱ组及慢性子宫颈炎组（P＜0.05）,而Cx43蛋白表达水平低于CINⅢ组、CINⅠ～Ⅱ组及慢性子宫颈炎组（P＜0.05）;Skp2的阳性表达与子宫颈癌分化程度、淋巴结转移有关（P＜0.05）;Cx43的表达缺失与淋巴结转移有关（P＜0.05）;子宫颈癌组织中Skp2和Cx43的表达呈负相关。结论　Skp2与Cx43的表达程度与子宫颈癌的发生、发展密切相关,且两者之间可能存在相互作用。     

胃癌中Cks1 、p27 Kip1和Skp2 蛋白的表达

 目的 探讨Cks1在胃癌发生及其在Skp2调节p27 ^Kip1降解过程中的作用。方法 应用流式细胞术测定正常胃粘膜和胃癌组织中Cks1、p27^Kip1、Skp2蛋白表达。结果胃癌组织中Cks1、Skp2表达明显高于正常胃粘膜（x²=22．69，P〈0．05；x²=13．42，P〈0．05），而p27 ^Kip1表达则低于正常胃粘膜（x²=14．83，P〈0．05）。胃癌中Cks1、Skp2表达与p27 ^Kip1表达呈负相关（r=-0．649，P〈0．05；r=-0．732，P〈0．05）；而Cks1蛋白表达与Skp2蛋白缺乏相关性（P〉0．05）。胃癌中Cks1的表达与肿瘤分化程度相关（x²=5．05，P〈0．05），而与肿瘤浸润深度、淋巴结转移及临床分期不相关（P〉0．05）。结论Cks1可能参与了胃癌的发生；胃癌中Cks1可能参与了Skp2调节p27 ^Kip1泛素化降解过程。     

PTEN、p27蛋白在胃癌组织中的表达及其相关性

 目的　研究胃癌组织中PTEN和p27蛋白的表达及二者间的相关性。方法　应用免疫组织化学方法检测49例胃癌组织、49例癌旁组织和13例正常胃黏膜中PTEN和p27蛋白的表达情况。结果　胃癌组织中PTEN和p27蛋白的阳性表达率分别为61.22 %（30／49）和57.14 %（28／49）,较癌旁组[91.84 %（45／49）、93.88 %（46／49）]和正常组织[100 %（13／13）、100 %（13／13）]明显降低（均P＜0.05）。两者在胃癌中的表达有相关性（r＝0.580,P＝0.000）,且均与肿瘤的分化程度、淋巴结转移和PTNM分期有关。结论　PTEN和p27基因的异常改变可能参与胃黏膜细胞的恶性转化过程,且两者之间存在相关性。联合检测两者表达水平可作为评价胃癌病理生物学行为的客观指标之一。     

胃癌和转移淋巴结组织ADAMTS1表达及其生物学意义的探讨

目的:探讨含(I)型血小板结合蛋白基序的解聚蛋白样金属蛋白酶( ADAMTS1)在胃癌及转移淋巴结组织中的表达,分析其与胃癌浸润深度、分化程度及淋巴结转移等临床病理学参数的关系.方法:免疫组化法检测72例成对胃癌组织、癌旁组织及胃周淋巴结组织标本ADAMTS1的表达,半定量评分系统评估染色,分析ADAMTS1表达与胃癌临床病理学参数的关系.结果:ADAMTS1在胃癌组织中弱阳性率、阳性率及强阳性率分别为37.5％(27/72)、4.2％(3/72)和1.4％(1/72),在癌旁组织中分别为58.3％(42/72)、25.0％(18/72)和11.1％(8/72),在转移淋巴结组织中分别为55.9％(33/59)、20.3％(12/59)和3.4％(2/59),在无转移淋巴结组织中分别为46.2％(6/13)、0(0/13)和0(0/13).胃癌组织ADAMTS1表达明显低于癌旁组织,z=-6.481,P＜0.000 1;转移淋巴结组织ADAMTS1表达明显高于胃癌组织(z=4.164,P＜0.000 1)和无转移淋巴结组织(z=2.130,P=0.033).ADAMTS1在有淋巴结转移的胃癌组织中表达明显高于无淋巴结转移的胃癌组织,z=2.045,P=0.041.结论:ADAMTS1在胃癌原发灶中呈现低表达,在转移淋巴结中呈现高表达.ADAMTS1在胃癌中表达与淋巴结转移有关,表明ADAMTS1基因表达在胃癌原发肿瘤生长及转移中可能存在不同的作用机制,可能与肿瘤微环境有关.     

Skp2和p27蛋白在乳腺癌中表达及临床意义

 目的 探讨Skp2与p27蛋白在乳腺癌中的表达及临床意义。方法 采用免疫组织化学方法对50例乳腺癌和12例正常乳腺组织中Skp2与p27蛋白表达水平进行研究。结果 乳腺癌中Skp2和p27蛋白表达水平与正常乳腺组织比较有显著差异(P<0．05)。Skp2与p27蛋白的表达水平与乳腺癌的临床分期、腋淋巴结受累及远处转移显著相关(P<0．05)；肿瘤大小，c-erbB-2表达，局部复发与p27蛋白表达水平显著相关，与Skp2表达无显著相关。Skp2与p27蛋白在乳腺癌中的表达呈负相关(P<0．05)。结论 Skp2与p27蛋白在乳腺癌的发生、发展及预后中起重要作用，对判断肿瘤的生物学行为和预后具有参考价值。     

Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas

Previous studies have shown that low levels of p27(KIP1), an inhibitor of G1 cyclin-dependent kinases (CDK), are associated with high aggressiveness and poor prognosis in a variety of cancers. Decreased levels of p27(KIP1) are caused, at least in part, by an acceleration of degradation with Skp2 (S-phase kinase-associated protein 2) and Jab1 (Jun activation domain-binding protein 1). This investigation was undertaken to examine whether the Skp2 and Jab1 expression is correlated with p27(KIP1) protein levels, and how it is clinically relevant in oral squamous cell carcinoma (OSCC). The correlations between p27(KIP1) and Skp2, and p27(KIP1) and Jab1 expression were evaluated by Western blot analysis. Immunohistochemical analysis was done in 75 cases of OSCC. A strongly significant inverse correlation was found between levels of p27(KIP1) and Skp2, and p27(KIP1) and Jab1 (p < 0.0001). Thus, decreased levels of p27(KIP1) were associated with strongly increased levels of Skp2 and Jab1, whereas high levels of p27(KIP1) coincided with low levels of Skp2 and Jab1. Reductions of p27(KIP1) expression and overexpression of Skp2 and Jab1 were significantly associated with cervical lymph node metastasis and poor prognosis. Overexpression of Skp2 and Jab1 is associated with the reduction of p27(KIP1) expression, and may have a role in the progression of OSCC.