Expression of Skp2 and its Relationship with VEGF and MVD in Colorectal Carcinoma / 胃肠病学

Background:In recent years,the incidence and mortality of colorectal carcinoma have been increasing rapidly. Diagnosing and treating cancer at gene level have become a new effective approach. Aims:To investigate the expression of S-phase kinase-associated protein 2(Skp2)and its relationship with vascular endothelial growth factor(VEGF)and tumor microvessel density(MVD)in colorectal carcinoma. Methods:Thirty-five colorectal carcinoma patients from March 2014 to March 2015 at People’s Hospital of Hubei University of Medicine were enrolled. Fifteen para-cancerous tissue samples were served as controls. The expressions of Skp2,VEGF and MVD value were determined by immunohistochemical SP, and their relationships with clinicopathological characteristics were analyzed. Results:The expression of Skp2 in colorectal carcinoma was significantly higher than that in para-cancerous tissue( P = 0. 000),and was correlated with tumor differentiation and lymph node metastasis(P 0. 05). Expression of VEGF and MVD value were significantly higher than those in para-cancerous tissue(P = 0. 019,P = 0. 002),and were correlated with lymph node metastasis and TNM stage(P < 0. 05). Expression of Skp2 was positively correlated with the expression of VEGF and MVD value in colorectal carcinoma( r = 0. 569,P = 0. 000;r = 0. 481,P = 0. 017 ). Conclusions:The abnormal high expression of Skp2 is involved in the angiogenesis of colorectal carcinoma. Skp2,VEGF expressions and MVD value may be served as important markers for malignancy degree of colorectal carcinoma.

Expression of P27kip1 and Skp2 in basal cell carcinoma and its clinical pathological characters / 国际肿瘤学杂志

Objective To investigate the expression of Skp2 and P27kip1 and their relationship with the clinicopathologic characters in basal cell carcinoma(BCC). To explore their expression between with the types of BCC of skin, especially in morpheaform BCC group. Methods Immunohistochemical SP technique was used to examine the expression of Skp2 and P27kip1 in 50 cases of BCC and 30 cases of normal tissues of skin.The expression level was analyzed combined with clinicopathological features of age, sex and types of tumor.Results Skp2 positive products located in cytoplasm or nucleus. P27kip1 positive products located in nucleus.The high expression of Skp2 and the low expression of P27kip1 were observed in BCC, there was statistical significance between the tumor group and the control group (P ＜ 0. 05 ) . The expression of Skp2 and P27kip1 were correlated with clinical types of BCC ( P ＜ 0. 05 ), while which were not correlated with age and sex ( P ＞0.05 ). In BCC tissue, Skp2 expression was negatively correlated with P27kip1 ( - 0.624; P ＜ 0.05), there was no correlated with each other in morpheaform BCC group ( P ＞ 0. 05 ). Conclusion The expression of Skp2 and P27kip1 in BCC are significant differences to normal skin tissues, and they are correlated with each other.They may play an important role in carcinogenesis and the development of BCC, and also make targets to treat it. Compared to nodular and superficial BCC group, the expression of Skp2 are higher in morpheaform BCC group, and the expression of P27kip1 is lower. They may play an important role in the types of the BCC and useful factors to predict the types of the tumor, also determine surgical margin for BCC cases.

S phase kinase-associated protein 2 regulates rat mesangial cells proliferation / 中华肾脏病杂志

Objective To explore whether the change of S phase kinase-associated protein 2 (Skp2) expression could regulate mesangial cell proliferation. Methods Skp2 siRNA and control siRNA, pIRES-GFP-Skp2 plasmid and pIRES-GFP plasmid were designed and synthesized. Cell transfection was performed by Lipofectamine 2000. Skp2 mRNA and protein levels were detected by semiquantitative PCR and Western blotting respectively. Primary culture rat mesangial cells were divided into 6 groups: 0%FCS, 20%FCS, 10%FCS+pIRES-GFP plasmid, 10%FCS+pIRES-GFP-Skp2 plasmid, 20%FCS+control siRNA, 20%FCS+Skp2 siRNA. Cell number was detected by MTT. S phase entry was measured by BrdU labeling. Cell cycle profile was determined by flow cytometric analysis. Results Skp2 mRNA level was significantly down-regulated by Skp2 siRNA compared to control siRNA. Skp2 protein level increased after pIRES-GFP-Skp2plasmid transfection compared to pIRES-GFP plasmid. MTT, BrdU labeling and cell cycle profile demonstrated that cell number (A: 0.419±0.088 vs 0.305±0.036, P＜0.01) and S-phase cells (BrdU labeling positive cell: 0.21±0.04 vs 0.15±0.03, P＜0.01;S-phase cell number:20.18±0.64vs 14.33±0.37, P＜0.01) obviously increased after Skp2 plasmid transfection, while decreased after Skp2 siRNA transfection compared to control groups (A: 0.328±0.069 vs 0.482±0.133, P＜0.01;BrdU labeling positive cell: 0.17±0.01 vs 0.24±0.00, P＜0.01; S-phase cell number: 16.52±0.75vs 23.81 ±1.25, P＜0.01). Conclusion Over-expression of Skp2 stimulates mesangial cell proliferation while down-regulated expression of Skp2 inhibits mesangial cell proliferation.

Expression and significance of Skp2 and Cx43 in cervical carcinoma / 肿瘤研究与临床

Objective To investigate the expression of Skp2 and Cx43 in cervical carcinoma and to study their relationships and clinical significance. Methods The expression of Skp2 and Cx43 was examined by immunohistochemical method in 48 cases of cervical carcinoma tissue, 84 cases of cervical intraepithelial neoplasia (CINⅠ - Ⅱ 45 cases, CINⅢ 39 cases), 28 cases of chronic cervicitis. Results Skp2 expression in cervical carcinoma was higher than that in the CINⅠ - Ⅱ and chronic cervicitis (P <0.05), Cx43 expression was lower in cervical carcinoma than that in the CINⅢ, CINⅠ - Ⅱ and chronic cervicitis (P <0.05). The expression of Skp2 was correlated with histological differentiation and lymph node metastasis (P <0.05). The expression of Cx43 was correlated with the lymph node metastasis (P <0.05). Besides, the expression of Skp2had a negative correlation with that of Cx43. Conclusion Skp2 and Cx43 may play an important role in the genesis and development of cervical carcinoma.

The Effect of Rosiglitazone on the Cell Proliferation and the Expressions of p27 and Skp2 in Helicobacter pylori Infected Human Gastric Epithelial Cells / 대한소화기학회지

BACKGROUND/AIMS: Ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the ligand-activated nuclear receptor superfamily, exhibit anti-tumoral effects and are associated with de novo synthesis of proteins involved in regulating the cell cycle and cell survival/death. Helicobacter pylori (H. pylori) is an etiologic agent for gastric adenocarcinoma, and raises the cell turnover of gastric epithelium. The aim of this study was to investigate the effect of PPAR gamma ligand rosiglitazone on the cell proliferation and the expressions of p27 and Skp2 protein in H. pylori infected gastric epithelial cells. METHODS: We examined the expression of PPAR gamma by Western blot in H. pylori infected AGS human gastric epithelial cells. The effect of rosiglitazone on the survival of H. pylori infected AGS cells was assessed by cell viability assay. After the treatment of rosiglitazone in H. pylori infected AGS cells, the expressions of p27 and Skp2 were assessed by Western blot. RESULTS: The expression of PPAR gamma protein was increased in H. pylori infected AGS cells. Cell growth was inhibited and decreased in dose- and time- dependent manner in H. pylori infected AGS cells treated with rosiglitazone. A decrease in Skp2 expression and a reciprocal increase in p27 expression were found in dose- and time-dependent manner in H. pylori infected AGS cells treated with rosiglitazone. CONCLUSIONS: Rosiglitazone inhibited the growth of H. pylori infected AGS cells. Rosiglitazone attenuated Skp2 expression, thereby promoting p27 accumulation in H. pylori infected human gastric epithelial cells. Further studies will be needed to find the effects of accumulation on cell turnover in H. pylori infection and the role in the H. pylori-associated gastric carcinogenesis.

Skp2 and malignandes / 白血病·淋巴瘤

S-phase kinase associated protein (Skp2) assumes the high expression in the most of malignant tumors, with its occurrence, and the development and the prognosis is closely related with a latent diagnose and treat went value. This review will focus on unique feature, biology activity, the function mechanism and with malignant tumor relations of the Skp2.

Expression of S-phase kinase associated protein 2 (Skp2) and E2F1 and its clinicopathological significance with rhinosinus squamous cell carcinoma / 中国医师杂志

Objective To study the clinicopathological significance of Skp2 and E2F1 in the rhinosinus squamous cell carcinoma and chronic sinusitis. Methods Immunohistochemical method was used to detect the expression of Skp2 and E2F1 in the routinely paraffin-embed-ded sections of specimens from patients with rhinosinus squamoas cell carcinoma (n=49), chronic sinusitis (n=28). Results The expres-sive positive rates and scores of Skp2 and E2F1 in rhinosinus sqnamous cell carcinoma were significantly higher than those in chronic sinusitis (P<0.01). The expression positive rates and scores were significantly decreased in middle-differentiated rhinosinus squamous cell carcino-ma. The maximal diameter of mass was less than 3cm, and no-metastasis of lymphnode or no-infiltration of regional rhinosinus can be found in T1N0M0. While in the low-differentiated rhinosinus squamous cell carcinoma, the maximal diameter of mass was larger than 3cm, and metasta-sis of lymphnode or infiltration of regional rhinosinus can be found(T3N1M0,T3N2M0) (P<0.01). The closely positive correlation was found between the expression of Skp2 and E2F1 in the rhinosinus squamoas cell carcinoma. Conclusions Skp2 and E2F1 might be important biologi-cal markers for carcinogenesis, progression, biological behaviors and prognosis of rhinosinus squamous cell carcinoma.

Expression of S-phase kinase associated protein 2 in liver tissues of rats with acute liver failure / 中华传染病杂志

Objective To investigate the expression of S-phase kinase associated protein 2 (Skp2) in rats with acute liver failure (ALF) and its significance. Methods There were 256 male SD rats used in this study, among which 240 were injected with D-galactosamine (D-GaIN) to set up ALF model. The rats were divided into 3 groups: ALF model group, free hepatocellular transplantation group, microencapsulated hepatocyte transplantation group, which were intraperitoneally injected with 2 mL of RPMI 1640 culture medium, free hepatocellular suspension and microencapsulated hepatocyte suspension, respectively. The other 6 rats were in control group and the rest 10 rats were used for hepatocyte isolation. Expressions of Skp2 protein in hepatocytes of rats at different time points were detected by immunohistochemical technique. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) were detected by automatic biochemistry analyzer. The survival rate in each group was observed. Comparisons among groups were done using one-factor analysis of variance. Results Levels of ALT, AST and TBil decreased more significantly by intraperitoneal transplantation of microencapsulated hepatocytes than those by intraperitoneal transplantation of free hepatocytes (P<0. 05). Skp2 labeling indices after 36 h of injection in ALF model group, free hepatocellular transplantation group and microencapsulated hepatocyte transolantation grouo were (28. 2±6.1) %, (41.4± 10. 5) % and (68. 0±10.8) %, respectively (F=29. 08 , P<0. 05). There were 4, 6 and 11 out of 15 rats survived in the 3 groups, respectively. Conclusion The dynamic observation of Skp2 expression could be used to judge the regeneration of hepatocytes.

Function mechanism and research development of Skp2 in malignant tumors / 肿瘤研究与临床

Skp2 (S-phase kinase associated protein) is substrate recognition subunit of SCFSkp2 (Cul1-Rbx1-Skp1-F boxSkp2)complex,a kind of ubiquitin ligases (E3s). Skp2 involves in regulating many functions of cell,such as cell cycle progressing,cell proliferation and differentiation,as well as apoptosis.At present many studies indicated that Skp2 is closely related to tumorigenesis and prognosis.With deeper study of Skp2 in tumor, Skp2 has the potential to be a promising drug target and biomarker of prognosis in human cancer.

S Phase Kinase Associated Protein 2 Expression in Breast Cancer and Its Prognostic Implications

BACKGROUND: S Phase Kinase Associated Protein 2 (Skp2), an F-box protein necessary for DNA replication, has recently been demonstrated to be an oncogene. The purpose of this study was to examine the Skp2 expression and to investigate its association with expressions of estrogen receptor (ER), androgen receptor (AR) and HER-2, as well as clinicopathological variables including tumor recurrence. METHODS: The expressions of Skp2, ER and AR were examined by immunohistochemistry and HER-2 amplification by chromogenic in situ hybridization (CISH) in 117 cases of breast carcinoma. RESULTS: Skp2 was expressed in 26 patients (22.2%) and was significantly correlated with tumor type (p=0.031), tumor grade (p=0.017) and ER expression (p=0.038). Twenty four (20.5%) of 117 patients had a tumor recurrence, and 6 patients (5.1%) died of multifocal metastases. Tumor recurrence was significantly correlated with histological grade (p=0.041) and lymph node status (p<0.001). CONCLUSIONS: Although Skp2 expression was statistically insignificant in association with tumor recurrence, it might be useful as a biologic predictor in breast cancer. The simple and reliable immunohistochemical assay presented in this study can be a routine part of breast cancer evaluation and may influence patient management.