PURPOSE: Cyclins, and their associated cyclin dependent kinases, regulate progression of the cell cycle through the G1 phase and into the S-phase during the DNA replication process. Cyclin E regulation is an important event in cell proliferation. Despite its importance, abnormalities of these genes and their protein products have yet to be found in lits asoociation with lung cancer. MATERIALS AND METHODS: The relationships between expression of cyclin A, cyclin B1, cyclin D1, cyclin D3, and cyclin E and clinicopathologic factors were investigated in 103 cases with non-small cell carcinomas, using immunohistochemical analysis. RESULTS: The positive immunoreactivity was observed in 51 cases (50%) for cyclin A, 33 cases (32%) for cyclin B1, 83 cases (81%) for cyclin D1, 19 cases (18%) for cyclin D3, and 11 cases (11%) for cyclin E. Expression of cyclin E was significant for lymph node metastasis (p=0.004, Chi-square test). There was no relationship between cyclin A, B1, D1, and E and histological typing, tumor size, lymph node metastasis, or pathological tumor, node and metastasis staging. CONCLUSION: These findings suggest that the expression of cyclin E played a role, to some degree, in the lymph node metastasis.
Adenocarcinoma ; Carcinoma, Squamous Cell ; Cell Cycle ; Cell Proliferation ; Cyclin A ; Cyclin B1 ; Cyclin D1 ; Cyclin D3 ; Cyclin E ; Cyclin-Dependent Kinases ; Cyclins ; DNA Replication ; G1 Phase ; Lung ; Lung Neoplasms ; Lymph Nodes ; Neoplasm Metastasis

<b>OBJECTIVEb>To 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).

<b>METHODSb>The 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.

<b>RESULTSb>Three 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).

<b>CONCLUSIONb>Cyclins 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

PURPOSE: To evaluate changes in expression of cell cycle related genes during apoptosis induced in HL60 cells by X-irradiation to understand molecular biologic aspects in mechanism of radiation therapy. MATERIAL AND METHODS: HL-60 cell line (promyelocytic leukemia cell line) was grown in culture media and irradiated with 8 Gy by linear accelerator (6 MV X-ray). At various times after irradiation, ranging from 3 to 48 hours were analyzed apoptotic DNA fragmentation assay for apoptosis and by western blot analysis and semi-quantitative RT-PCR for expression of cell cycle related genes (cyclin A, cyclin B, cyclin C, cyclin D1, cyclin E, cdc2, CDK2, CDK4, p16INK4a, p21WAF1, p27KIP1, E2F, PCNA and Rb). RESULTS: X-irradiation (8 Gy) induced apoptosis in HL-60 cell line. Cycline A protein increased after reaching its peak 48 h after radiation delivery and cyclin E, E2F, CDK2 and RB protein increased then decreased after radiation. Radiation induced up-regulation of the expression of E2F is due to mostly increase of phosphorylated retinoblastoma proteins (ppRb). Cyclin D1, PCNA, CDC2, CDK4 and p16INK4a protein underwent no significant change at any times after irradiation. There was not detected p21WAF1 and p27KIP1 protein. Cyclin A, B, C mRNA decreased immediately after radiation and then increased at 12 h after radiation. Cyclin D1 mRNA increased immediately and then decreased at 48 h after radiation. After radiation, cyclin E mRNA decreased with the lapse of time. CDK2 mRNA decreased at 3 h and increased at 6h after radiation. CDK4 mRNA rapidly increased at 6 to 12 h after radiation. There was no change of expression of p16INK4a and not detected in expressin of p21WAF1 and p27KIP1 mRNA. CONCLUSION: We suggest that entry into S phase may contribute to apoptosis of HL60 cells induced by irradiation. Increase of ppRb and decrease of pRb protein are related with radiation induced apoptosis of HL60 cells and tosis of HL60 cells induced by irradiation. Increase of ppRb and decrease of pRb protein are related with radiation induced apoptosis of HL60 cells and this may be associated with induction of E2F and cyclinE/CDK2. These results support that p21WAF1 and p27KIP1 are not related with radiation induced-apoptosis.
Apoptosis* ; Blotting, Western ; Cell Cycle* ; Culture Media ; Cyclin A ; Cyclin B ; Cyclin C ; Cyclin D1 ; Cyclin E ; Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclins ; DNA Fragmentation ; HL-60 Cells* ; Humans ; Leukemia ; Particle Accelerators ; Proliferating Cell Nuclear Antigen ; Retinoblastoma Protein ; RNA, Messenger ; S Phase ; Up-Regulation

<b>OBJECTIVEb>To characterize the human primary cyclins (D1, E, A, B1) expressed in gastric carcinoma, and to clarify the relationship between the types of expressed primary cyclins and clinicopathological features of gastric carcinoma.

<b>METHODSb>Primary cyclins (D1, E, A, B1) expressed in single cells separated from 68 cases gastric carcinoma tissues were analyzed by flow cytometry. We classified the gastric carcinomas by different types of the expressed primary cyclins, and explore the roles of primary cyclins expressed in cell cycle and the expression patterns of the cyclins. The results were analyzed together with clinicopathological features.

<b>RESULTSb>The patterns of expressed primary cyclins could be classified into five types. The proportion was 10.3% (7/68), 22.1% (15/68), 25.0% (17/68), 29.4% (20/68), and 13.2% (9/68), respectively, from type I to type V. Each type could be, according to the degree of in-cycle cyclins expressed, divided into different sub-types. The types of primary cyclins expressed were strongly linked to invasive depth and lymph node metastasis of the gastric carcinoma (P < 0.01). The rates of lymph node metastasis were 26.6%, 43.8%, 82.3%, 95.0%, and 100.0%, respectively, from type I to type V. The type of primary cyclins expressed was also significantly associated with disease stage (TNM stage). The proportion of stage IV disease was 0, 6.7%, 17.6%, 25.0% and 55.6%, respectively, from type I to type V. It was shown that there were relationships between the sub-types of primary cyclins expressed and different growth-types, degree of cell differentiation, or, the tumor gross types (P < 0.01).

<b>CONCLUSIONSb>The types of primary cyclins expression are different in the process of the occurrence, development and metastasis of gastric carcinoma, and are correlated with clinicopathological features of gastric carcinoma.

Adult ; Aged ; Aged, 80 and over ; Cell Differentiation ; Cyclin A1 ; metabolism ; Cyclin B1 ; metabolism ; Cyclin D1 ; metabolism ; Cyclin E ; metabolism ; Cyclins ; classification ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Oncogene Proteins ; metabolism ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVE: Cyclin is a family of regulatory proteins that play a key role in controlling the cell cycle. Abnormalities of cell cycle regulators, including cyclins and cyclin dependent kinases (CDKs), have been reported in malignant tumors. This study was undertaken to quantitatively detect cyclin B1 and D1 in cervical cancer. METHODS: A quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to analyze the expression of cyclin B1, D1 mRNA and proteins, respectively, in fresh invasive cervical cancer (n=41) and normal cervix tissue (n=10). RESULTS: There was significantly greater cyclin B1 expression in invasive cervical cancer than in normal cervix tissue (p=0.019). However, cyclin D1 expression was not significantly different (p=0.967). A Western blot analysis yielded similar results. CONCLUSION: Our results were consistent with the concept that up-regulation of cyclin B1 expression occurred in cervical cancer and an aberrant expression of cyclin B1 might play an important role in cervical carcinogenesis.
Blotting, Western ; Carcinogenesis ; Cell Cycle ; Cervix Uteri ; Cyclin B1* ; Cyclin D1 ; Cyclin I ; Cyclin-Dependent Kinases ; Cyclins* ; Female ; Humans ; RNA, Messenger ; Up-Regulation ; Uterine Cervical Neoplasms*

Cell growth characterized by cell cycle progression is regulated by cyclin-dependent kinase (CDK). CDKs are activated by binding cyclins such as cyclin A, cyclin B, cyclin D1, and cyclin E. Proliferative indices such as Ki-67 and proliferative cell nuclear antigen (PCNA) are known to be correlated with the mitotic index and were reported to have increased in the lesional psoriatic skin in previous reports. In this study, we investigated the expression of cyclins and proliferative indices (cyclin A, cyclin B, cyclin D1, cyclin E, Ki-67, and PCNA) in the psoriatic epidermis before and after cyclosporin therapy (3mg/kg/day 12 wks). Cyclin A, Ki-67, and PCNA were 1+ to 2+ positive before treatment but showed positive staining in only a few cells after treatment. Cyclin B and cyclin E were also moderate-to-strongly positive before treatment and became only weakly positive after treatment. Cyclin D1 was expressed only in a few cells and was negative after treatment. Taken together, cyclosporin may have an anti-proliferative effect on keratinocytes which was demonstrated by reduction of the proliferative indices such as Ki-67 and PCNA. The mechanism of the anti-proliferative effect may be through the inhibition of the cell cycle progression. Cyclin A, cyclin B and cyclin E are amongst the targeted cell cycle modulators, whereas cyclin D1 seems to be less induced in the lesional psoriatic epidermis, both before and after cyclosporin therapy.
Cell Cycle ; Cyclin A ; Cyclin B ; Cyclin D1 ; Cyclin E ; Cyclins* ; Cyclosporine* ; Epidermis* ; Keratinocytes ; Mitotic Index ; Phosphotransferases ; Proliferating Cell Nuclear Antigen ; Psoriasis ; Skin

<b>OBJECTIVEb>To clarify the role of these cyclins in human gastric cancer.

<b>METHODSb>38 gastric cancer patients, 29 first degree relatives of gastric cancer patients, as well as 18 healthy subjects were included. The mRNA expression of cyclins D1, D2, D3 and E in gastric biopsies was evaluated by RT-PCR analysis using specific primers. Histomorphological features such as intestinal metaplasia, atrophy, H. pylori infection and severity of gastritis were determined by the updated Sydney System.

<b>RESULTSb>Significant mRNA overexpression was found for cyclins D2, D3 and E compared with healthy normal specimen, but cyclin D1 expression was not different between tumor and normal tissues. In addition, cyclin D2 and D3 overexpression was significantly more frequent in first degree relatives than in healthy controls (P < 0.05). Among the various pathological findings, the overexpression of cyclins D2 and E was associated with intestinal metaplasia, and the overexpression of cyclin D3 was associated with intestinal metaplasia as well as atrophy. The overexpression of cyclins D2 and D3 was significantly correlated with H. pylori infection. No correlation was observed between the overexpression of cyclin D1 and any pathological variables.

<b>CONCLUSIONb>The overexpression of cyclins D2, D3 and E is a frequent event in patients with gastric cancer and their first degree relatives and may be an early event in gastric carcinogenesis.

Adult ; Aged ; Aged, 80 and over ; Cyclin D1 ; genetics ; Cyclin D2 ; Cyclin D3 ; Cyclin E ; genetics ; Cyclins ; genetics ; Family Health ; Gastritis ; genetics ; Gene Expression Regulation, Neoplastic ; Helicobacter Infections ; genetics ; microbiology ; Helicobacter pylori ; growth & development ; Humans ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Stomach ; metabolism ; microbiology ; pathology ; Stomach Neoplasms ; genetics ; pathology

Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Cervi Parvum Cornu(CPC) have been traditionally used as an hale, growth, hematogenous, anti-aging, back pain in Eastern medicine. The purpose of present study was to investigate the effects of CPC extract on cell cycle progression and its molecular mechanism in human fetal osteoblasts. CPC extracts (10 microgram/ml) increased cell proliferation in the human fetal osteoblasts as compared to non-supplemented control. There was no significant change in the G1 and S phase, but a increase in the G2/M phase in 10 microgram/ml and 100 microgram/ml of CPC extracts group as compared to non-supplemented control. The protein expression of cyclin E, cdk 2, cyclin D, cdk 4, and cdk 6 was higher than that of control group. The level of p21 was lower than that of control. But that of pRb and p16 was not distinguished from control. These results indicate that the increase of cell proliferation by CPC extracts may be due to the increased expression of cyclin E , cdk 2, cyclin D, cdk 4 and cdk 6, and the decreased expression of p21 in human fetal osteoblasts .
Back Pain ; Cell Cycle* ; Cell Proliferation ; Cyclin D ; Cyclin E ; Cyclins ; Humans* ; Osteoblasts* ; S Phase

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

Fibroblasts are major cellular components of gingiva and periodontal ligament. They regulate the healing process after surgery or injury. Recently, many natural medicines, whose advantages are less side effects and possibility of long-term use, have been studied for their capacity, their anti-bacterial and anti-inflammatory effects and regenerative potential of periodontal tissues. Sophorae radix have been traditionally used as an antibacterial and anti-inflammatory drug in oriental medicine. The purpose of present study was to investigate the effects of Sophorae radix extract on cell cycle progression and its molecular mechanism in human gingival fibroblasts. Sophorae radix extracts(100microgram/ml) notably increased cell proliferation and cell activity in the human gingival fibroblasts as compared to non-supplemented controls. There was an increase in the S phase and a decrease in the G1 phase in 100microgram/ml of Sophorae radix extracts group as compared to non-supplemented controls. The level of cyclin E and cdk 2 protein in test group was higher than that of control groups. But that of cyclin D, cdk 4, and cdk 6 was not distinguished from controls. The level of p53 protein in test group was lower than that of controls, whereas that of p21 was not different. The level of pRB protein in test group was higher than that of controls, whereas that of p16 was lower. These results indicate that the increase of cell proliferation by Sophorae radix extracts may be due to the increased expression of cyclin E and cdk 2, and the decreased expression of p53 and p16 in human gingival fibroblasts.
Cell Cycle Proteins* ; Cell Cycle* ; Cell Proliferation ; Cyclin D ; Cyclin E ; Cyclins ; Fibroblasts* ; G1 Phase ; Gingiva ; Humans* ; Medicine, East Asian Traditional ; Periodontal Ligament ; S Phase ; Sophora*