Correlation Between cyclin G1 Expression and Efficacy of Radiotherapy on Primary Hepatocellular Carcinoma / 肿瘤防治研究

Objective To investigate the correlation between cyclin G1 expression and the efficacy of radiotherapy on HCC. Methods The expression of cyclin G1 in biopsy specimens of 68 patients who received radiotherapy was detected by immunochemistry. The correlation between cyclin G1 expression and clinicopathological characteristics was analyzed by chi-square test. The correlation between cyclin G1 expression and OS or PFS was evaluated by Kaplan-Meier analysis. Univariate and multivariate analyses were used for the relation between clinicopathological characteristics and OS or PFS. Results The expression of cyclin G1 was related to portal vein tumor embolus, clinical stage and alpha fetoprotein. Survival analysis showed that the OS and PFS of patients with low expression of cyclin G1 were significantly higher than those with high cyclin G1 expression (P < 0.05). Multivariate analysis showed that cyclin G1 was an independent risk factor for DFS of patients with HCC. Conclusion High expression of cyclin G1 is an adverse prognostic factor for HCC patients who received radiotherapy.

Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression

Breast cancer is the most common cause of cancer among women in most countries (WHO). Ovarian hormone disorder is thought to be associated with breast tumorigenesis. The present study investigated the effects of estrogen and progesterone administration on cell proliferation and underlying mechanisms in breast cancer MCF-7 cells. It was found that a single administration of estradiol (E2) or progesterone increased MCF-7 cell viability in a dose-dependent manner and promoted cell cycle progression by increasing the percentage of cells in the G2/M phase. A combination of E2 and progesterone led to a stronger effect than single treatment. Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells. After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA, estradiol- and progesterone-mediated cell viability and clonogenic ability were significantly limited. Additionally, estradiol- and progesterone-promoted cell accumulation in the G2/M phase was reversed after knockdown of cyclin G1. These data indicated that estrogen and progesterone promoted breast cancer cell proliferation by inducing the expression of cyclin G1. Our data indicated that novel therapeutics against cyclin G1 are promising for the treatment of estrogen- and progesterone-mediated breast cancer progression.

Molecular mechanisms of Cyclin G1 involving in the replication of hepatitis viruses and development of hepatocellular carcinoma / 中华实验和临床病毒学杂志

Cyclin G1 is a new member of the Cyclin G family, while it is not the main molecule for regulating cell cycle functionally. Cyclin G1 has been found to play important roles in the replication of hepatitis viruses and development of hepatocelluar carcinoma(HCC). This paper aims to review the research progress on the characteristics of Cyclin G1 protein sequence, the interaction of Cyclin G1with microRNA, the roles and mechanisms of Cyclin G1 in the replication of HBV and HCV as well as the development of HCC, which might provide the theoretical basis and new research insights for the related diseases.

The role ofΔ133p53 during 5-FU inhibition experiments on the growth of gastric cancer cell line MKN45 / 中国癌症杂志

Background and purpose:Δ133p53 can promote tumor cell growth, but the exact mechanism is not clear. This study was aimed to observe the expression and signiifcant of the p53 isoformsΔ133p53 and p53 gene downstream molecules MDM2 and cyclin G1 genes by 5-FU-MKN45 gastric cancer cell line model. Methods:Af-ter using different concentrations of 5-FU (50μg/mL, 100μg/mL) to human gastric cancer cell line MKN45, inhibition rate should be detected by MTT assay, the changes ofΔ133p53 mRNA, MDM2 mRNA and cyclin G1 mRNA express-ing were detected by reverse transcription-polymerase chain reaction (RT-PCR). Differences between these groups were analyzed by ANOVA, comparisons within groups were analyzed by t-test, bivariate correlation was analyzed by Pearson linear correlation. Results:MTT results showed that with the increased concentration of 5-FU and the extension of time, the cell inhibition rates increased gradually. The inhibition rates of 50μg/mL 5-FU were 41.10%, 54.79%and 68.48%, for culturing 24, 48 and 72 hours. There were statistically signiifcant differences between the groups(F=45.52, P=0.00). The inhibition rates of 100μg/mL 5-FU were 69.53%, 78.21%and 86.92%, for culturing 24, 48 and 72 hours. There were statistically signiifcant differences between the groups(F=85.58,P=0.00). The inhibition rates of 50 and 100μg/mL were 41.10%and 69.53%, for culturing 24 hours. There were statistically signiifcant differences between the groups(F=51.29, P=0.00). The inhibition rates of 50 and 100μg/mL were 54.79%and 78.21%, for culturing 48 hours. There were statistically signiifcant differences between the groups(F=51.29, P=0.00). The inhibition rates of 50 and 100μg/mL were 68.48%and 86.82%, for culturing 72 hours. There were statistically signiifcant differences between the groups(104.91, P=0.00). RT-PCR results showed that with the increase of the concentration of 5-FU, theΔ133p53 mRNA, MDM2 mRNA and cyclin G1 mRNA expression gradually declined in gastric cancer cell line MKN45 cells, and there were statistically signiifcant differences between the groups(F=738.532, 1 396.607, 2 785.56,P=0.00). Cor-relation analysis showed that the expressions ofΔ133p53 mRNA and MDM2 mRNA in gastric cancer were positively correlated (r=0.871, P=0.01), while the expression of cyclin G1 mRNA and p53 mRNA had no obvious relevance (P=0.13). Conclusion:In the 5-FU-MKN45 gastric cancer cell line model, anti-tumor pathway ofΔ133p53 isomers is related with MDM2 but was not related with cyclin G1.

Effects of low-dose γ-ray on the expression of CCNG1 gene in human lymphoblasts / 解放军医学杂志

Objective To investigate the effects of low dose γ-ray on the gene expression of cyclin G1 (CCNG1) in human lymphoblasts AHH-1 line and the probability of CCNG1 as bio-dosimeter for low-dose radiation. Methods Lymphoblasts of AHH-1 line were irradiated with γ-ray in the doses of 0, 0.1, 0.2, 0.5, 0.8 or 1.0 Gy. Total RNA of cells was extracted at 0, 4, 24, 48, 72 and 168h after irradiation, and real-time Q-PCR was used to detect the expression of CCNG1 gene in AHH-1 cells. The relationship between the irradiation dosage or duration and the gene expression was analyzed. Results The gene expression of CCNG1 in AHH-1 cells increased in a dose-dependent manner after irradiation, presenting a better dose-effect relationship. Time-effect curve indicated that the peak expression of CCNG1 appeared at 24h after irradiation, and then the expression decreased gradually with time, and it recovered to the level before irradiation at 168h after irradiation. Conclusions CCNG1 gene is sensitive to low dose irradiation (0-1.0Gy) with a better dose and time-effect relationship, and it may be used as a potential efficient biological dosimetry in low dose exposure risk assessment.

Changes in expression of cell cycle regulators after G1 progression upon repetitive thioacetamide treatment in rat liver

Repetitive low dose thioacetamide (TA) treatment of hepatocytes was found to induce cells in G2 arrest. In the present study, an attempt was made to investigate alterations in expression of cell cycle regulators after G1 progression in the same repetitive low dose TA treated hepatocytes system and to define the determinators involved in G2 arrest. TA was daily administered intraperitoneally, with a dose of 50 mg/kg for 7 days. Expression levels of cyclin E and CDK2 were similar, increased at day 1 and reached a peak at day 2. And they recycled from day 3 reaching a second peak at day 5. Expression level of cyclin A was similar to p27(Kip1) and p57(Kip2) but not to CDK2 and increased to a peak level at day 2. Expression levels of cyclin B1 and cdc2 were similar although the cyclin B1 level was generally low, decreased from day 1 to basal levels at day 3 and persisted at a low level till day 7. The expression level of cyclin G1 was similar to p53 that peaked at day 3 and again at day 6 elevated over basal level. BrdU-labeled hepatocytic nuclei increased from 12 h, reached a peak at day 2, then decreased, and were not detectable from day 6. The number of PCNA-labeled nuclei increased immediately, peaked at day 2, and maintained till day 7. These results suggest that G2 arrest induced by repeated TA treatment might be p53-dependent, via activation of cyclin G1, rather than inhibition of cyclin B1- cdc2 complex, and inhibitors holding S phase progression might be p27(Kip1) and p57(Kip2).