OBJECTIVE: The objective of this study was to evaluate the relationship between the expression of cyclin B1, D1 and the various prognostic factors in ovarian carcinoma. METHODS: In this study, fresh ovarian tissue samples were obtained from 41 patients treated surgically at our institute from March of 2002 to February of 2005. These included 36 ovarian carcinomas and 5 normal ovarian tissues that were served as the control. Quantitative real-time RT-PCR and Western blot analysis were used in detecting the expression of mRNA and protein of cyclin B1, D1, respectively. RESULTS: The mean 2(-delta delta CT) values of cyclin B1 and D1 mRNA in ovarian carcinoma tissues obtained through quantitative real-time RT-PCR were 5.83+/-12.03, 17.60+/-22.20, respectively, and the mean values in the control were 0.55+/-0.35, 0.50+/-0.26, respectively. The results showed difference in the expression, but were not statistically significant (p=0.67, 0.07, respectively). If the mean densitometer value of cyclin B1 and D1 protein in the control obtained by Western blot analysis was 1, the mean values in ovarian carcinoma tissues were higher, but were not statistically significant (1.30+/-0.73, 1.81+/-1.28, respectively) (p=0.76, 0.06, respectively). The expression of cyclin B1, D1 and various prognostic factors was not statistically related. CONCLUSION: Our results showed that the expression of cyclin B1 and D1 in ovarian carcinoma tissues was higher than in the normal control. This suggested that cyclin B1, D1 and the tumorigenesis and the degree of malignancy was closely related. But the expression of cyclin B1, D1 and various prognostic factors was not statistically related. Further studies based on the correlation between cyclin and response to treatment or survival rate are needed to support cyclin as a prognostic factor of ovarian carcinoma.
Blotting, Western ; Carcinogenesis ; Cyclin A ; Cyclin B1* ; Cyclin D1 ; Cyclins* ; Humans ; RNA, Messenger ; Survival Rate

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*

OBJECTIVE: To determine whether Indole-3-carbinol (I3C) can enhance the inhibitory effect of genistein on a human uterine leiomyoma cells. METHODS: Five uterine leiomyoma tissues were obtained from hysterectomies conducted on the benign diseases and cultured primarily. MTS reduction assay was carried out to determine the viability of human uterine leiomyoma cells. Cell cycle analysis for I3C and genistein treated human uterine leiomyoma cells was done by Fluorescent activated cell sorter (FACS) analysis. To detect the presence and expression of cell cycle related proteins was done by Western blot analysis. RESULTS: I3C and genistein induced growth inhibition in a dose dependent manner, treatment with 100 micro mol/L I3C and 100 micro mol/L genisten blocked 60% cell growth. FACS results showed that treatment with the I3C and genistein increased the percentage of cells in G2/M phase and decreased S phase. From Western blot analysis it revealed I3C and genistein induced the expression of p53, p21, and p27 increasing. Reduced expression of cyclin B1 and cyclin E were detected in treatment with I3C and genistein. The expression levels of these proteins correlate with G2/M cell cycle arrest. Activation of caspase pathway and fragmentation of PARP did not take place. CONCLUSIONS: These results demonstrate that I3C enhances genistein-mediated uterine leiomyoma cell growth inhibition through the cell cycle arrest at G2/M phase by decreasing the production of cyclin B1. Because of the synergistic effect of I3C and genistein, the potential exists for the therapeutic efficacy of each phytochemical when used in combination.
Blotting, Western ; Cell Cycle ; Cell Cycle Checkpoints ; Cyclin B1 ; Cyclin E ; Cyclins ; Genistein* ; Humans* ; Hysterectomy ; Leiomyoma* ; S Phase

BACKGROUND: Oncogene expression in Paget's disease of the breast is not well known. To characterize invasive ductal carcinoma associated with Paget's disease, we studied expression of anaphase promoting complex (APC) with its regulatory proteins. METHODS: Immunohistochemical stainings were done with 10 cases of invasive ductal carcinoma associated with Paget's disease for APC, pituitary tumor transforming gene (PTTG), cyclin B1, p53, cyclin D1, and c-erbB-2. The expressions of these markers in Paget's disease were compared with those in the associated with carcinoma. RESULTS: APC, PTTG, cyclin B1, and c-erbB-2 were positive in all of the cases with both Paget's disease and underlying carcinoma. p53 was expressed in Paget's disease of 6 cases (60%) and in carcinoma of 7 cases (70%). Cyclin D1 was positive in Paget's disease of 8 cases (80%) and in carcinoma of 9 cases (90%). CONCLUSIONS: Breast carcinomas with Paget's disease seem to be distinguished by the high expression of APC, cyclin B1, PTTG, c-erbB2, and cyclin D1 in contrast to breast cancers without Paget's disease. Furthermore, the similar expression patterns of APC and APC regulatory proteins in both Paget's disease and underlying breast cancer support the epidermotropic theory as its pathogenetic mechanism.
Anaphase* ; Anaphase-Promoting Complex-Cyclosome* ; Breast ; Breast Neoplasms ; Carcinoma, Ductal* ; Cyclin B1 ; Cyclin D1 ; Oncogenes ; Paget's Disease, Mammary ; Pituitary Neoplasms

OBJECTIVETo confirm the unscheduled in vivo and in vitro expression models of cyclin B1 in cancer cells so as to study the different profiles of cyclin B1 in G(1)-phase immortal cells under different culture states and culture conditions.

METHODSMultiparameter flow cytometry (FCM) was used to correlate the expression of cyclin B1 with the position in cell cycle of immortal cells in vivo and in vitro using the MOLT-4 cell line as control. Cells which belonged to G(1)-phase were sorted by FCM according DNA diploidy, and then the expression of cyclin B1 was examined by confocal microscope to confirm the results. For further analysis, different subgroups in G(1) phase were sorted according to the fluorescent intensity of cyclin E, and then the exact period in G(1) phase when cyclin B1 was expressed, were assayed by Western blot.

RESULTSUnscheduled expression of cyclin B1 expressed in G(1)-phase was found not only in synchronized leukemia cells MOLT-4 and in vivo transformed T-7 cells, but also in vivo tumor cells detached from clinical samples. In the synchronized growing cells, cyclin B1 was mainly detected in the early G(1) phase, while in transformed T7 cells, cyclin B1 was mainly detected in the late G(1) phase.

CONCLUSIONThe limitation of detecting cyclin B1 is due to its unscheduled expression, rending cyclin B1 being detected at different time-spots in the G(1) phase. This phenomenon may be related to the adjustment between the loss of control in cell proliferation and cell apoptosis, thereby leading to tumorigenesis.

Apoptosis ; physiology ; Cell Line, Transformed ; Cyclin B ; biosynthesis ; Cyclin B1 ; Flow Cytometry ; G1 Phase ; physiology ; Humans ; Tumor Cells, Cultured

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

An FDA approved drug for the treatment of type II diabetes, Troglitazone (TRO), a peroxisome proliferator–activated receptor gamma agonist, is withdrawn due to severe idiosyncratic hepatotoxicity. In the search for new applications of TRO, we investigated the cellular effects of TRO on YD15 tongue carcinoma cells. TRO suppressed the growth of YD15 cells in the MTT assay. The inhibition of cell growth was accompanied by the induction of cell cycle arrest at G₀/G₁ and apoptosis, which are confirmed by flow cytometry and western blotting. TRO also suppressed the expression of cell cycle proteins such as cyclin D1, cdk2, cdk4, cyclin B1, cdk1(or cdc2), cyclin E1 and cyclin A. The inhibition of cell cycle proteins was coincident with the up-regulation of p21(CIP1/WAF1) and p27(KIP1). In addition, TRO induces the activation of caspase-3 and caspase-7, as well as the cleavage of PARP. Further, TRO suppressed the expressions of Bcl-2 without affecting the expressions of Bad and Bax. Overall, our data supports that TRO induces cell cycle arrest and apoptosis on YD15 cells.
Apoptosis ; Blotting, Western ; Caspase 3 ; Caspase 7 ; Cell Cycle Checkpoints ; Cell Cycle Proteins ; Cyclin A ; Cyclin B1 ; Cyclin D1 ; Cyclins ; Flow Cytometry ; Peroxisomes ; Tongue* ; Up-Regulation

BACKGROUND: It has been reported that p53 regulates the G2-M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The aim of this study is to clarify the role of the cell cycle regulators, cyclin B1 and p53 in patients with esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHOD: Tissue samples from 46 patients with ESCC were included in this study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemical study. RESULT: Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 10% of tumor cells were cyclin B1 positive in 19 patients (41.3%). Several clinicopathologic parameters, including tumor stage (p<0.05), pathologic lymph node status (p<0.05) and invasion of lymphatic vessels (p<0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also correlated with a poor prognosis in patient with ESCC in univariate analysis (p<0.05) and multivariate analysis (p<0.05). In contrast, p53 expression exhibited significant correlation with the level of cyclin B1 expression, but was not associated with prognostic parameters in patients with ESCC. CONCLUSION: These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC.
Carcinoma, Squamous Cell* ; Cell Cycle ; Cyclin B1* ; Cyclins* ; Epithelium ; Esophageal Neoplasms ; Esophagus ; Humans ; Lymph Nodes ; Lymphatic Vessels ; Multivariate Analysis ; Prognosis

BACKGROUND: Cell cycle deregulation plays a major role in chemical multistage carcinogenesis.Therefore, the evaluation of cell cycle proteins is important. METHODS: In order to induce carcinogenesis in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)was administered to male Sprague-Dawley rats for 30 weeks. Expressions of cyclin D1, A, E, and B1 were examined by immunohistochemical stainings. RESULTS: Urothelial cell hyperplasia appeared at 5 weeks, followed by papilloma at 10 weeks. Superficial carcinoma was observed at 20 weeks, and invasive carcinoma developed in 40% (4/10) of the rats at 30 weeks. Expressions of cyclin D1 and A increased sequentially from normal mucosa throughhyperplasia, papilloma, and carcinoma (p<0.01). Expressions of cyclin D1, B1 and cyclin Ewere higher in invasive carcinomas than in superficial carcinomas (p<0.01). In contrast, therewas no significant difference in the expression of cyclin B1 between hyperplasia, papillomaand superficial carcinoma. CONCLUSIONS: The present results indicate the important roles of cyclin D1 and A in the development of BBN-induced urothelial carcinoma of rats. Aberrantexpression of cyclin B1 and E may contribute to the progression from superficial to invasivebladder cancer rather than tumorigenesis.
Animals ; Carcinogenesis* ; Cell Cycle ; Cell Cycle Proteins ; Cyclin B1 ; Cyclin D1 ; Cyclins* ; Humans ; Hyperplasia ; Male ; Mucous Membrane ; Papilloma ; Rats* ; Rats, Sprague-Dawley ; Urinary Bladder*

PURPOSE: Disturbance in normal cell cycles by cell cycle control factors is an important process of cancer carcinogenesis. The aims of this dissertation were identify the influence of cyclin B1 and D1 on the growth and expression of gastric cancer and their effects on the prognosis. METHOD: The subjects were 128 patients selected from those who underwent gastric surgery for their gastric cancer between January 1995 and December 1998. Immunohistochemical staining was conducted for cyclin B1 and D1 using paraffin embedded tissues, followed by analysis of their protein expressions, possible prognostic factors and survival rate. RESULTS: Cyclin B1 expression was founded in 48 of the 128 patients (37.5%), and that of cyclin D1 in 96 (75%). Both cyclin B1 and D1 showed no statistical significance with T-stage, location of tumors or histologic types. However, for the case of any significance with lymph node metastasis, the higher the N-stage, the greater was the expression of cyclin B1 (P=0.014). For the case of any significance with life term, the Kaplan-Meier method showed the greater the expression of cyclin B1, the shorter the life term (P=0.042). CONCLUSION: An association was indicated between cyclin B1 and lymph node metastasis in gastric cancer, but has no relation with the T-stage, histologic type or location of tumors. Cyclin D1 shows no association with lymph node metastasis, T-stage, histologic type or location of tumors. However, cyclin B1 showed a significant association with the survival rate.
Carcinogenesis ; Cell Cycle ; Cell Cycle Checkpoints ; Cyclin B1* ; Cyclin D1 ; Cyclins* ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Paraffin ; Prognosis ; Stomach Neoplasms* ; Survival Rate*