OBJECTIVETo investigate the expression of human telomerase reverse transcripase (hTERT), cyclin D1 mRNA, p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein in human ameloblastoma (ABs).

METHODSThe expression of hTERT, cyclin D1, p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein in 54 cases of human ABs were detected by in situ hybridization or immunohistochemistry.

RESULTSThe positive cases of hTERT mRNA, cyclin D1 mRNA was 51, 23, respectively. The positive cases of p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein was 17, 12, 9. Comparing with recurred and transformed malignantly, the expression of hTERT mRNA, cyclin D1 mRNA increased, and the expression of p16(INK4), p21(WAF1) mRNA and p27(KIP1) protein decreased or lost. The expression of hTERT mRNA and pl6(INK4), p21(WAF1) mRNA and p27(KIP1) protein in ABs had middle to high negative relation (r(k) = -0.587, r(k) = -0.652, r(k) = -0.783, P < 0.001).

CONCLUSIONThe hTERT mRNA expression in ABs is related to the reguation of pl6(INK4), p21(WAF1) mRNA and p27(KIP1) protein.

Ameloblastoma ; Cyclin D1 ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclins ; Humans ; Immunohistochemistry ; RNA, Messenger ; Telomerase

PURPOSE: p27Kip1 protein is an inhibitor of cyclin-dependent kinases and is thought to be a potential prognostic indicator for numerous human cancers. We investigated the expression of p27Kip1 in gastric cancer in order to estimate its clinical utility. METHODS: Immunohistochemical assay for p27Kip1 protein was performed in 64 patients with primary gastric cancer. The correlation between p27Kip1 and clinical-biological parameters including patient survival was analyzed. RESULTS: p27Kip1 expression was suppressed in 40 (62.5%) of 64 gastric cancer patients. Expression of p27Kip1 was significantly reduced in poorly differentiated cancers (82.1%, 23/28; P=0.015) and was also reduced in tumors with a high S-phase fraction as compared with tumors showing a low S-phase fraction (86.7%, 26/30, 41.2%, 14/34; P=0.0002). In univariate analysis, the extent of the disease (P<0.001), and reduced expression of p27Kip1 (P=0.0006) were statistically significant to predict the patient's outcome, however depth of invasion (P=0.008) and pathologic stage (P=0.009) emerged as significant prognostic indicators in the multivariate analysis. CONCLUSION: The expression of p27Kip1 is closely linked with cell proliferation and differentiation of human gastric cancer. p27Kip1 appears to have potential as a prognostic marker in the management of gastric cancer patients.
Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p27* ; Cyclin-Dependent Kinases ; Humans* ; Immunohistochemistry ; Multivariate Analysis ; Prognosis ; Stomach Neoplasms*

PURPOSE: The cyclin-dependent kinase inhibitor p27kip1 protein is a negative regulator of the cell division cycle, and its degradation is required for entry into the S phase. Loss of p27(kip1) protein expression has been reported to be associated with aggressive behavior in a variety of tumors of epithelial and lymphoid origin. The purpose of this study was to determine the expression of p27 protein in adenoma and adenocarcinoma of the colorectum and to assess the prognostic significance. METHODS: We performed immunohistochemical staining for expression of p27 protein in adenomas (20 cases) and adenocarcinomas (30 cases) of the colorectum. The data (p27 protein labeling index (LI, mean+/-standard deviation)) were analyzed in association with clinicopathologic parameters. RESULTS: p27 protein LI of normal mucosa (10 cases), adenoma, and adenocarcinoma were 93.3+/-4.5, 65.4+/-17.5, and 28.2+/- 14.5, respectively (p<0.0001). p27 protein LI of well differentiated adenocarcinoma was slightly higher than those of moderately and/or poorly differentiated adenocarcinoma, but did not show any significant difference among these groups (p=0.19). Also p27 protein expression did not show any significant relationship to other prognostic facters such as age, invasion depth, and operative staging. CONCLUSIONS: The results suggested that reduced expression of p27 protein may play an important role in the malignant transformation process of colorectal cancer.
Adenocarcinoma* ; Adenoma* ; Cell Cycle ; Colorectal Neoplasms ; Cyclin-Dependent Kinase Inhibitor p27 ; Mucous Membrane ; Phosphotransferases ; S Phase

p27Kip1 has been recognized as a negative regulator of cell cycle. Reduced level of p27 expression is associated with development and aggressiveness of several human tumors. To investigate the role of p27Kip1 on progression of colorectal adenocarcinoma, we studied 40 cases of human colorectal adenocarcinomas for expression of p27Kip1 protein using an immunohistochemical method, and compared these results with known prognostic parameters of colorectal adenocarcinoma. Among 40 cases of colorectal adenocarcinomas, p27Kip1 expression was detected in the nuclei of tumor cells in 14 cases (35%). The expression rate of p27Kip1 protein was significantly lower in the cases with lymph node metastasis (25.8%) than in those without lymph node metastasis (66.6%) (p<0.05). But it did not correlate with other parameters such as tumor size, histologic grade, vascular invasion, and Ki-67 labeling index. The results suggest that reduced expression of p27Kip1 protein plays a role in biologically aggressive behavior of colorectal adenocarcinoma.
Adenocarcinoma* ; Cell Cycle ; Cyclin-Dependent Kinase Inhibitor p27* ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis

This study was purposed to explore the expression of P27(kip1)and cyclin G in patients with acute leukemia (AL) and its correlation. The reverse polymerase chain reaction (RT-PCR) was used to analyse the expression of P27(kip1) and cyclin G mRNA in 89 AL patients and 10 normal persons; Western blot was used to analyze the expression of P27(kip1) and cyclin G protein in 39 AL patients and 10 normal persons. The results showed that the cyclin G mRNA and protein expressions in new diagnosed/relapsed cases of AL were significantly higher than those in patients with remission and normal controls (p < 0.05 and p < 0.01), but there was no difference between remission cases and normal controls (p > 0.05). The expression of P27(kip1) mRNA in newly diagnosed/relapsed patients with AL was not significantly different from patients with remission and normal controls (p > 0.05), while the P27(kip1) protein expression in remission cases of AL and normal controls was significantly higher than that in new diagnosed/relapsed cases (p < 0.05), but there was no difference between remission cases and normal controls (p > 0.05). The expression of P27(kip1) negatively and lowly correlated with the expression of cyclin G in patients with AL. It is concluded that the low expression of P27(kip1) and the high expression of cyclin G in patients with AL may have some correlation with genesis and development of AL and may be an indication for poor prognosis of AL.
Adult ; Cyclin G1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Female ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male

OBJECTIVE: The cyclin-dependent kinase inhibitor p27kip1 protein is a negative regulator of the cell cycle, and its degradation is required for entry into the S phase. Loss of p27kip1 expression has been reported to be associated with aggressive behavior in a variety of tumors of epithelial and lymphoid origin. However, its association with various astrocytic tumors has not been clearly demonstrated. We studied to investigate the relationship of p27kip1 expression with the biological behavior of astrocytic tumors in addition to study on the role of p27kip1 in the tumorigenesis of these tumors. PATIENTS AND METHODS:From 1990 to 1998, a total of 29 astrocytic tumor of all grades obtained by operative resection were included for evaluation. We studied the expression of p27kip1 protein immunohistochemical assay in astrocytic tumors and compared the findings with the clinicopathologic parameters. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections by the avidin-biotin-peroxidase complex method. According to WHO classification, all cases were divided into astrocytomas(4 cases), anaplastic astrocytomas(9 cases), and glioblastomas(16 cases) by 3 pathologists. Clinical information was obtained from medical records, and others such as location and size of tumors from imaging studies. RESULTS: Mean p27kip1 protein labeling indexes(LI, mean+/-standard deviation) of astrocytomas, anaplastic astrocytomas, and glioblastomas were 80.6+/-9.1, 63.6+/-21.0, and 28.9+/-18.7, respectively, and were inversely correlated with grade of glial tumors(p<0.0001). Mean p27kip1 protein LI in the recurrent group was lower than that in the non-recurrent group, but there was no significant difference statistically(p=0.464). Additionally, p27kip1 protein expression did not show any significant relationship to other prognostic factors such as age(p=0.1643), tumor size(p=0.8), or location(p=0.8). CONCLUSION: These results suggested that reduced expression of p27kip1 protein may play a important role in the malignant transformation process of astrocytic tumor cells.
Astrocytoma ; Carcinogenesis ; Cell Cycle ; Classification ; Cyclin-Dependent Kinase Inhibitor p27* ; Glioblastoma ; Humans ; Medical Records ; Phosphotransferases ; S Phase

OBJECTIVETo evaluate the correlation of p27 protein expression in the cytoplasm with the clinicopathologic features of nasopharyngeal carcinoma (NPC).

METHODSImmunohistochemistry was employed to examine P27 protein expression in the cytoplasm of NPC samples and nasopharyngeal (NP) tissue samples. The differential expression of P27 protein between NPCs and NPs and the correlation of cytoplasmic P27 protein expression with the clinicopathologic parameters of NPC patients was analyzed. RESULTS Immunohistochemistry indicated significantly down-regulated t p27 protein expression in NPC tissues compared to that in NP tissues (P=0.047). The reduction of P27 expression was inversely correlated with T classification of NPC (P=0.033). Although cytoplasmic p27 protein expression was not significantly correlated with lymph node metastasis (P=0.157) or clinical stages of NPC (P=0.090), an obvious trend of inverse correlations between them was noted.

CONCLUSIONDown-regulated cytoplasmic p27 protein expression may promote the carcinogenesis of NPC and can be an unfavorable prognostic factor for survival of NPC patients.

Carcinoma ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Cytoplasm ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Prognosis

Pituitary tumors are usually benign but can occasionally exhibit hormonal and proliferative behaviors. Dysregulation of the G1/S restriction point largely contributes to the over-proliferation of pituitary tumor cells. F-box protein S-phase kinase-interacting protein-2 (SKP2) reportedly targets and inhibits the expression of p27(Kip1), a well-known negative regulator of G1 cell cycle progression. In this study, SKP2 expression was found to be upregulated while p27(Kip1) expression was determined to be downregulated in rat and human pituitary tumor cells. Furthermore, SKP2 knockdown induced upregulation of p27(Kip1) and cell growth inhibition in rat and human pituitary tumor cells, while SKP2overexpression elicited opposite effects on p27(Kip1) expression and cell growth. The expression of microRNA-186 (miR-186) was reported to be reduced in pituitary tumors. Online tools predicted SKP2 to be a direct downstream target of miR-186, which was further confirmed by luciferase reporter gene assays. Moreover, miR-186 could modulate the cell proliferation and p27(Kip1)-mediated cell cycle alternation of rat and human pituitary tumor cells through SKP2. As further confirmation of these findings, miR-186 and p27(Kip1) expression were downregulated, while SKP2 expression was upregulated in human pituitary tumor tissue samples; thus, SKP2 expression negatively correlated with miR-186 and p27(Kip1) expression. In contrast, miR-186 expression positively associated with p27(Kip1) expression. Taken together, we discovered a novel mechanism by which miR-186/SKP2 axis modulates pituitary tumor cell proliferation through p27(Kip1)-mediated cell cycle alternation.
Animals ; Cell Cycle ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p27 ; Genes, Reporter ; Humans ; Luciferases ; Pituitary Neoplasms ; Rats ; Up-Regulation

BACKGROUND/AIMS: The cyclin-dependent kinase inhibitors (CDKI) including p21, p27, and p57 of the kinase inhibitor protein (KIP) family are negative regulators of cell cycle progression and potentially act as tumor suppressor. Tumor behavior and growth are influenced by the extent of tumor cell proliferation. The aim of this study was to evaluate the expression of KIP family CDKI in gastric cancer tissue, and to examine the relationship between these expression and various clinicopathological parameters including tumor cell proliferation. METHODS: We conducted an immunohistochemical analysis of p21, p27, and p57 expression in 109 gastric cancer tissues. Tumor cell proliferation was assessed by immunohistochemistry with antibody against Ki-67. RESULTS: Negative expression of p21, p27, and p57 was demonstrated in 45.9%, 65.1%, and 57.8% of cancer tissues, respectively. Negative expression of p21 correlated with larger tumor size, poor differentiation, depth of invasion, lymph node metastasis and advanced TNM stage (p=0.048, 0.041, 0.001, 0.005, and 0.001 respectively). Negative expression of p21 correlated with poor survival (p=0.037). Tumors with negative p21 expression had higher Ki-67 expression than those with positive p21 expression (p=0.024). No significant correlation could be observed between status of p27 and p57 expression and various clinicopathological parameters including survival and tumor cell proliferation. CONCLUSIONS: These results suggest that negative expression of p21 may play an important role in carcinogenesis by stimulating tumor cell proliferation, and may help in predicting the prognosis of gastric cancer.
Adult ; Aged ; Cell Division ; Cyclin-Dependent Kinase Inhibitor Proteins/*metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Cyclin-Dependent Kinase Inhibitor p57/metabolism ; English Abstract ; Female ; Humans ; Male ; Middle Aged ; Stomach Neoplasms/*metabolism/mortality/pathology ; Survival Rate

PURPOSE: To explore the role of cell cycle and apoptosis regulators during hepatocarcinogenesis, the expression of cell cycle-related proteins (cyclin D1 and p27kip1) and apoptosis-related proteins (p53, survivin, caspase 3). METHODS: Sprague-Dawley rats were given 120 ppm diethylnitrosamine (DEN) as a carcinogen and sequentially sacrificed. The expression of cell cycle and apoptotic related proteins were examined by light microscopy and immunohistochemistry. RESULTS: During the DEN-induced hepatocarcinogenesis, sequential histologic changes from preneoplastic lesions (altered hepatic cellular foci, hyperplastic nodules, and hepatocellular adenomas) and ultimately overt hepatocellular carcinomas and metastatic lesions were noted. The cyclin D1 were progressively increased from preneoplastic lesions to hepatocellular carcinomas. However, the p27kip1 and the survivine proteins did not show any other difference with the increasing degree of carcinogenesis. The p53 and caspase 3 proteins were more significantly increased in hepatocellular carcinomas than preneoplastic lesions. The cyclin D1 protein expression did not show any correlation with the expression of p27Kip1 protein, but the p53 expression was related to the expression of survivin and caspase 3. CONCLUSION: From the above results, over-expression of cyclin D1 plays a role in the early and late stages of hepatocarcinogenesis. In addition p53 and caspase 3 might be useful markers for evaluating the risk of malignant transformation.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Caspase 3 ; Cell Cycle ; Cyclin D1 ; Cyclin-Dependent Kinase Inhibitor p27 ; Diethylnitrosamine ; Light ; Microscopy ; Proteins ; Rats ; Rats, Sprague-Dawley