OBJECTIVETo investigate the expression of five kinds of cyclins in hepatocellular carcinoma (HCC) and their association with degree of tumor differentiation, metastasis and infection of hepatitis B virus (HBV).

METHODSThe HCC tissue microarrays were composed of those from 273 cases of HCC tissues, 144 surrounding-tumor liver tissues and 10 normal liver tissues obtained from autopsy. The diameter of each specimens on tissue microarrays was 2.0 mm. Immunohistochemistry was used to detect the expression of cyclin A, cyclin B, cyclin D1, cyclin D3 and cyclin E on HCC tissue microarrays. The association of the expression of these cyclins with the infection rate of HBV was also analyzed.

RESULTSThree paraffin-embedded HCC tissue microarrays were successfully constructed, including 136, 143 and 148 tissue spots, respectively. The positive rates of cyclins in 273 cases of HCC were cyclin A 52.7%, cyclin B 45.4%, cyclin D1 35.9%, cyclin D3 44.3% and cyclin E 23.1%; while the figures in 144 surrounding-tumor tissues were 8.3%, 5.6%, 4.9%, 6.3% and 1.4%, respectively. In 10 normal liver tissues these cyclins exhibited negative staining, with the exception that cyclin D1 was positive in one case of normal liver tissue. The positive rate of cyclins in HCC were significant higher than those in surrounding-tumor liver tissues (P < 0.01), in HCC tissues with histological grade II and III, the cyclins expression were stronger than that in grade I (P < 0.05). The positive rates of cyclins, except cyclin A in HCC with portal vein invasion were higher than those without portal vein invasion (P < 0.01). Infection of HBV did not have significant relationship with the expression of cyclins (P > 0.05).

CONCLUSIONCyclins in different cell cycles overexpressed at varied levels in hepatocellular carcinoma, and the increased expression of cyclins may shorten the tumor cell cycle phase, accelerate cell proliferation, and have a close relationship with HCC aggressiveness.

Carcinoma, Hepatocellular ; chemistry ; Cyclin A ; analysis ; Cyclin B ; analysis ; Cyclin D1 ; analysis ; Cyclin D3 ; Cyclin E ; analysis ; Cyclins ; analysis ; Hepatitis B ; metabolism ; Humans ; Immunohistochemistry ; Liver Neoplasms ; chemistry

OBJECTIVES: The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. METHODS: Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. RESULTS: Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. CONCLUSION: These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.
Adult ; Age Factors ; Animal ; Blotting, Western ; Cell Cycle ; Cells, Cultured ; Comparative Study ; Cyclin A/analysis ; Cyclin B/analysis ; Cyclin D1/analysis ; Cyclin E/analysis ; Cyclin-Dependent Kinases/analysis* ; Cyclins/analysis* ; Female ; Fetal Development ; Heart Atrium/growth & development* ; Heart Atrium/embryology ; Heart Atrium/cytology* ; Heart Atrium/chemistry ; Human ; Male ; Middle Age ; Myocardium/chemistry* ; Rats ; Rats, Sprague-Dawley ; Substances: Cyclin D1 ; Substances: Cyclins ; Substances: Cyclin-Dependent Kinases ; Substances: Cyclin E ; Substances: Cyclin B ; Substances: Cyclin A

OBJECTIVETo contrast the feature of different periods of p53, p16, and cyclin D1 expression in cells of hepatocarcinoma.

METHODSSixty hepatocarcinoma specimens were collected and divided into three periods in one yearly cycle with each period of 20 cases. Hepatocellular carcinoma was documented in all cases by pathomorphological classification. Edmondson-Steinet grading belonged to II~III stages. The expression of gene proteins of p53, p16, and cyclin D1 was determined by immunohistochemical assay (S-P method). The expressive intensity was analysed by the rank test.

RESULTSp16 expression showed significant difference of period (H=10.334, P<0. 05). Arpil-July was the high expressive period.

CONCLUSIONSp16 may take an important role in the chronobiologic mechanism of gene control of hepatocyte canceration and hepatocarcinoma cell growth.

Carcinoma, Hepatocellular ; chemistry ; Cyclin D1 ; analysis ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms ; chemistry ; Male ; Middle Aged ; Tumor Suppressor Protein p53 ; analysis

Cyclin D1, a G1 cyclin, has been implicated in the oncogenesis of various types of malignancies via deregulation of cell cycles. Amplification of cyclin D1 as a part of 11q13 amplicon has been reported in lung cancer as well as a subset of carcinomas arising from various organs including breast, head and neck, and esophagus. In addition to its role as an oncogene, several recent studies have suggested that amplification is indicative of poor prognosis. In this study we examined the cyclin D1 protein expression in 102 consecutive cases of lung cancers using the microwave enhanced immunohistochemical staining method and correlated the data with the histologic subtype and grade, Ki-67 (MIB-1) labeling index, and survival. Nuclear positive staining was observed in 18 cases (18 %) of lung cancers. Although squamous cell carcinoma demonstrated a higher rate of expression (12 /58, 21%), three of 33 adenocarcinomas (9%) revealed overexpression and both adenocarcinoma and squamous cell carcinoma components within the adenosquamous carcinoma showed nuclear staining. There was no correlation between cyclin D1 overexpression and histologic grade, Ki-67 (MIB-1) labeling index, and survival. These observations indicate that cyclin D1 protein overexpression might be implicated in the oncogenesis of the various histologic types of non-small cell lung carcinomas but it has no usefulness as a prognostic marker.
Cyclin D1 ; Cyclins/*analysis ; Human ; Immunohistochemistry ; Lung Neoplasms/*chemistry/mortality/pathology ; Neoplasm Staging ; Oncogene Proteins/*analysis ; Support, Non-U.S. Gov't

OBJECTIVECyclinD1 and p21CIP1 are major proteins to regulate lung cell proliferation and involved in lung development and lung injury reparation. This study aimed to explore the expression manners of CyclinD1 and p21CIP1 at canalicular, saccular and alveolar stages during lung development in Sprague-Dawley rats.

METHODSLung tissues were obtained from fetal rats of 20 and 21 days gestational ages, and neonatal rats at 0, 3, 7, 14 and 21 days (n=6). Lung tissues were used for histopathology and the protein analysis of CyclinD1 and p21CIP1 (immunohistochemistry and Western blot).

RESULTSThe strongest expression of CyclinD1 and the weakest expression of p21CIP1 occurred at 20-21 days gestation (canalicular stage). At the canalicular stage, CyclinD1 was mainly expressed in epithelial cells, and the expression of p21CIP1was negative. At the saccular stage, the expression of CyclinD1 decreased significantly and the p21CIP1 expression increased significantly. Positive expression of CyclinD1 and p21CIP1 was found in epithelial cells and interstitial cells. At the alveolar stage, the CyclinD1 expression was the lowest and the p21CIP1 expression was the highest. The positive expression of CyclinD1 was found in interstitial cells and that of p21CIP1 was found in epithelial cells.

CONCLUSIONSThe location and quantity of CyclinD1 and p21CIP1 expression are different at various stages during lung development in rats. A strongest CyclinD1 expression found in the canalicular stage may be associated a high lung cell proliferation. A strongest p21CIP1 expression found in the alveolar stage may be associated with alveolar maturity.

Animals ; Blotting, Western ; Cyclin D1 ; analysis ; Cyclin-Dependent Kinase Inhibitor p21 ; analysis ; Female ; Immunohistochemistry ; Lung ; chemistry ; embryology ; Male ; Rats ; Rats, Sprague-Dawley

PURPOSE: The aim of this study was to determine the expressions of Rb, p16, and cyclin D1 in soft tissue sarcomas, and we also wanted to identify the prognostic factors according to the clinicalpathologic features. MATERIALS AND METHODS: We reviewed the charts and radiographic films of 66 sarcoma patients. Tissue samples were collected from these patients. Immunochemistry was performed using formalin-fixed, paraffin-embedded tissue samples to examine the expressions of p16, Rb, and cyclin D1 proteins. RESULTS: The median duration of overall survival was 47.8 months (range, 20.0 to 70.7 months) and the 5 years survival rate was 39%. As for the correlation between the degree of immunohistochemical staining for Rb protein and the histological tumor grades, there was a significant difference with a p-value of 0.019. However, no significant correlation was shown for p16 and cyclin D1. The overall survival duration of the Rb negative group (staining cell <20%) and the heterogeneous group (cell staining 20 to 80%) was 53.5+/-6.6 months and the overall survival duration of the Rb homogeneous group was 18.3+/-6.4 months, and there was a significant difference with a p-value of 0.016. However, no significant difference was shown between the survival rate according to the p16 and cyclin D1 expressions. On the multivariate analysis that was done with Rb, p16, the tumor size, grade and site, and patient age, the Rb gene expression was the most significant independent prognostic factor with a risk ratio of 3.01 (p=0.04). CONCLUSION: The expression of Rb protein was correlated with the histologic grade and overall survival of patients with soft tissue sarcomas.
Cyclin D1 ; Cyclins ; Genes, Retinoblastoma ; Humans ; Immunochemistry ; Multivariate Analysis ; Odds Ratio ; Proteins ; Retinoblastoma Protein ; Sarcoma ; Survival Rate ; X-Ray Film

OBJECTIVETo investigate the expression of cyclin D1, p16, AR and ER in fibroblasts of scars for further understanding the interaction of these factors and the roles that they play in scar development.

METHODSThirty samples of mature scar, hypertrophic scar and keloid were detected with immunohistochemical method (SP technique) and compared with normal skin.

RESULTSThere were on positive results in normal skin and mature scars. The expression of cyclin D1, p16 and AR was higher in hypertrophic scars and keloids than in normal skin with significant difference (P < 0.05). The expression of cyclin D1 in keloids was higher than in hypertrophic scars (P < 0.05). Though the expression of p16 was higher in keloids than in hypertrophic scars, the difference was not significant. There was significant correlation between the expression of cyclin D1 and AR in the pathologic scar.

CONCLUSIONThe AR played an important role in scar formation and displayed its function through cyclin D1. The expression of p16 could suppress the excessive proliferation of cells to some extent. If the effect was not enough to resist the function of cyclin D1, long-term proliferation of cells would occur and lead to keloid formation. As the expression of cyclin D1 and p16 in hypertrophic scars was in a state of relative equilibrium, the cell proliferation showed a tendency of self-restriction.

Cicatrix ; metabolism ; pathology ; Cyclin D1 ; analysis ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; metabolism ; Fibroblasts ; chemistry ; metabolism ; Humans ; Immunohistochemistry ; Receptors, Androgen ; analysis ; metabolism ; Receptors, Estrogen ; analysis ; metabolism ; Skin ; chemistry ; metabolism ; pathology

OBJECTIVETo investigate gene amplification of CCND1 and expression of cyclin D1 in hepatocellular carcinoma (HCC) and to explore the possible relationship between CCND1 gene status and carcinogenesis of HCC.

METHODSDifferential PCR, RT-PCR and immunohistochemistry were used to detect gene amplification, mRNA and protein expression of cyclin D1 in 20 HCC cases respectively. The relationship between the gene amplification rate and the expression level of cyclin D1 and the histological grades of HCC was analyzed.

RESULTSCCND1 gene amplification was detected in 30% of the cases HCC. An overexpression of cyclin D1 mRNA and protein could be demonstrated in 45% and 70% cases respectively. The expression of cyclin D1 mRNA correlated with its gene amplification status (P < 0.05) and was responsible for the protein expression level (P < 0.05). There was a close relationship between the expression level of cyclin D1 protein and HCC histological grades (P < 0.05).

CONCLUSIONSCCND1 gene amplification is a common phenomenon in HCC and may be directly responsible for the cyclin D1 mRNA and protein overexpression. Cyclin D1 protein expression level is directly related to HCC histological grades. Therefore, CCND1 amplification and cyclin D1 overexpression may play an important role in development and differentiation of HCC.

Adult ; Aged ; Carcinoma, Hepatocellular ; genetics ; Cyclin D1 ; analysis ; genetics ; Female ; Gene Amplification ; Humans ; Immunohistochemistry ; Liver Neoplasms ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; RNA, Messenger ; analysis

OBJECTIVETo investigate the clinicopathologic features of mantle cell lymphoma (MCL) and the significance of immunostaining for cyclin D1 in diagnosis.

METHODSClinicopathologic observation and immunohistochemical staining for CD20, CD45RO, cyclin D1, bcl-2, Ki-67, CD5 for 8 cases of mantle cell lymphoma were performed.

RESULTSThe 8 cases of mantle cell lymphoma consisted of 6 males and 2 females, aged from 43 to 78 years (mean 57 years). Histopathologically, MCL demonstrated architectural destruction by a vaguely nodular monomorphic lymphoid proliferation with vaguely nodular, diffuse or mantle zone growth patterns. Analogous to centrocytes, the lymphoma cells with slightly to markedly irregular nuclear contours showed moderately dispersed chromatin and a low mitotic figure. Three cases were transformed into highly aggressive blastoid variants. The tumor cells were positive for CD20, CD5, bcl-2 and cyclinD1 in all 8 cases and negative for CD45RO.

CONCLUSIONSThe clinicopathological features and special immunophenotypes were present in mantle cell lymphoma. This tumor can be differentiated from other small B-cell lymphomas on the basis of histopathologic features and positive cyclin D1 immunophenotype. The blastoid variant should also be differentiated from other variants.

Adult ; Aged ; Cyclin D1 ; analysis ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; analysis ; Lymphoma, Mantle-Cell ; diagnosis ; pathology ; Male ; Middle Aged ; Prognosis

To investigate the effects of estrogen (E2) on telomerase activity and its mechanism in human breast cancer cells, estrogen receptor positive MCF-7 cells were treated with different concentrations of E2. Telomerase activity was measured by using TRAP-ELISA method, the cell cycle phases analyzed by using flow cytometry, and the expression of Cyclin D1 detected by using immunohistochemistry method. The results showed that telomerase activity levels were increased in MCF-7 cells treated with 10(-8) mol/L E2 during the observed period (P < 0.05), and E2 increased telomerase activity levels in a dose-dependent manner(10(-10)-10(-8) mol/L); Simultaneously, the cell cycle phases of MCF-7 cells treated with 10(-8) mol/L E2 were changed significantly: G0/G1 phase decreased from 60.52% to 50.93%. S phase increased from 29.03% to 30.83%; However, the expression of Cyclin D1 was decreased. It was concluded that estrogen can upregulate telomerase activity of MCF-7 cells, and the effect can be blocked by antiestrogen tamoxifen. Its mechanism may be closely associated with modulation of cell cycle phases.
Breast Neoplasms ; chemistry ; enzymology ; pathology ; Cell Cycle ; Cyclin D1 ; analysis ; Estrogens ; pharmacology ; Female ; Humans ; Receptors, Estrogen ; analysis ; Telomerase ; genetics ; metabolism ; Tumor Cells, Cultured