• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.776-784
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• 1998

Background: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11q13) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore playa key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. Purpose: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. Method: Total 81 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from January 1, 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. Results : The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was $22.76{\pm}3.50$ months in cyclin D1 positive group and $45.38{\pm}5.64$ months in eyclin D1 negative group. There was a nearly significant difference in overall survival between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. Conclusion: Based on this study, cyelin D1 overexpression appears an important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.

• Journal of Animal Science and Technology
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• v.48 no.3
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• pp.353-360
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• 2006

This study was performed to investigate the effects of artificial stimulation on the increase of the oocyte activation, to evaluate the expression of cyclin B1 protein levels in enucleated mouse oocytes, and to investigate correlation between the oocyte activation and the cyclin B1 protein levels. The oocyte activation was induced by 7% ethanol (EtOH) or 10μg/ml Ca-ionophore with or without 10μg/ml cycloheximide (CH). The activation rate was significantly higher in both single (p<0.05) and combined (p<0.01) stimulated groups compared to control group. The cyclin B1 protein level was significantly reduced in both stimulated groups (p<0.05), except for EtOH+CH treatment group. The expression of cyclin B1 protein showed a higher negative correlation with activation rate in EtOH+CH (r=0.61, p<0.05) and Ca+CH (r=0.86, p<0.01) stimulation groups, but not in a both single stimulation groups. Taken together, it can be suggested that single (EtOH and Ca- ionophore) and combined (EtOH+CH and Ca+CH) stimulation increases the oocyte activation, especially combined stimulation, because it induces the degradation of cyclin B1 protein after artificial stimulation treatments in mouse oocytes.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.218-227
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• 2018

In this study, we investigated the effect of the extracts from Vaccinium oldhamii on cell proliferation and the regulatory mechanisms of cyclin D1 protein level in human cancer cells. The branch extracts from Vaccinium oldhamii (VOB) showed higher inhibitor effect against the cell growth than leave extracts (VOL) and fruit extracts (VOF) in human colorectal cancer, breast cancer, prostate cancer, non-small lung cancer, pancreatic cancer and liver cancer cells. In addition, VOB decreased cyclin D1 level at both protein and mRNA level. MG132 treatment attenuated VOB-mediated cyclin D1 downregulation. A point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by VOB. In addition, the inhibition of nuclear export by leptomycin B (LMB) attenuated cyclin D1 degradation by VOB. But, the treatment of PD98059 (ERK1/2 inhibitor), SB203580 (p38 inhibitor), SP600125 (JNK inhibitor), LiCl ($GSK3{\beta}$ inhibitor), LY294002 (PI3K inhibitor) or BAY 11-7082 ($I{\kappa}K$ inhibitor) did not affect VOB-induced cyclin D1 degradation. In conclusion, VOB induced cyclin D1 degradation through redistribution of cyclin D1 from the nucleus to cytoplasm via T286 phosphorylation of cyclin D1, which resulted in the inhibition of cancer cell proliferation.

• Reproductive and Developmental Biology
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• v.30 no.2
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• pp.115-118
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• 2006

Cyclin B1 is known to reflect the M-phase promoting factor (MPF), a universal regulator of G2/M-phase transition, activity during the process of oocytes maturation. To investigate whether culture condition affects the maturation rate and the expression of cyclin B1 protein, bovine immature oocytes are stimulated and cultured according to the following protocols: Experiment 1: denuded oocytes (denude) only, COC only, denuded oocytes+granulosa cells (denude+GCs) and COC+GCs; Experiment 2: no-activation (control), 7% ethanol for 5 min and $10{\mu}l/ml$ ionomycin for 5 min at immediately before maturation. The maturation rates of denude and no-activation group were significantly lower in both experiments (P<0.05), respectively. Co-culture or stimulation method in bovine immature oocytes culture increases the cyclin B1 expression significantly in both experiments (P<0.05). Based on these results, culture condition affects the maturation rate and the expression of cyclin B1 protein during the first meiotic maturation in bovine immature oocytes.

• Animal cells and systems
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• v.2 no.4
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• pp.495-500
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• 1998

D-type G1 cyclins are known to be crucial for the progression of mitotic cell cycle in mammals. Although many studies have been performed to elucidate the roles of D-type cyclins, it is largely unknown whether D-type cyclins are directly involved in the regulation of meiotic germ cell development. In the present study, we examined the expression patterns of D-type cyclins (cyclin D1 and D3) during male germ cell development by northern blot and in situ Hybridization analyses. In the adult testes, we detected a 4.2 kb cyclin D1 mRNA and two different sizes (2.3 kb and 1.8 kb) of cyclinD3 mRNAs. The short form of the cyclin D3 transcript was testis-specific. Along with the testicular development, expression of cyclin D3 mRNA was increased whereas cyclin D1 mRNA was gradually decreased. in situ hybridization study also revealed that the expression of cyclin D3 was restricted to the postmeiotic germ cells. Furthermore, the 2.3 kb transcript was highly expressed in the round spermatids and decreased in the elongated spermatids/residual bodies, while the 1.8 kb transcript was expressed in elongated spermatids/residual bodies more abundantly. Sucrose-gradient separation of polysomal RNA fractions demonstrated that some portions of the 2.3 kb transcript are translationally active, while the 1.8 kb transcript is likely to be inactive. Taken together, the present data suggest a functional importance of cyclin D3 expression in the differentiated postmeiotic male germ cells.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.264-269
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• 2018

Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. Mice lacking the tumor suppressors $p16^{Ink4a}$ (Cdkn2a, cyclin-dependent kinase inhibitor 2a), $p19^{Arf}$ (an alternative reading frame product of Cdkn2a,), and $p27^{Kip1}$ (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. The $p16^{Ink4a}$ and $p19^{Arf}$ knockout mice were generated via transcription activator-like effector nucleases (TALENs), and $p27^{Kip1}$ knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). These gene editing technologies were targeted to the first exon of each gene, to induce frameshifts producing premature termination codons. Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.94-98
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• 1997

Ceramide. a product of sphingomyelin hydrolysis, has been proposed as a lipid second messenger mediating antiproliferative activation. In this study, we examined the role of the cell cycle-related proteins in the ceramide-mediated growth suppression. Treatment of U-937 cells with C$_2$-ceramide(N-acetylsphingosine) resulted in growth suppression in a time- and concentration dependent manner. Ceramide induced concentration dependent dephosphorylation of retinoblastoma gene product (Rb). Rb remains hypophosphorylated in synchronized cells even after serum stimulation in the presence of ceramide. Ceramide decreased the expression of cyclin D$_1$ and cyclin E levels. These results suggest that antiproliferative effect of ceramide is associated with hypophosphorylation of Rb and decreased expression of cyclin D1 and cyclin E.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5207-5211
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• 2012

The present study was designed to explore the anti-cell proliferative efficacy of ferulic acid by analysing the expression pattern of cell proliferative markers, proliferating cellular nuclear antigen (PCNA) and cyclin D1, in the buccal mucosa of golden Syrian hamsters treated with 7,12-dimethylbenz(a)anthracene (DMBA). Oral squamous cell carcinomas developed in the buccal pouch of hamsters using topical application of 0.5% DMBA three times a week for 14 weeks. Immunohistochemical (PCNA) and RT-PCR (Cyclin D1) analysis revealed over expression of PCNA and cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone (tumor bearing hamsters). Oral administration of ferulic acid at a dose of 40 mg/kg bw to hamsters treated with DMBA not only completely prevented the tumor formation but also down regulated the expression of PCNA and cyclin D1. The results of the present study thus suggests that ferulic acid might have inhibited tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative potential as evidenced by decreased expression of PCNA and cyclin D1.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.994-1004
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• 2005

The dihydrofolate reductase (dhfr) promoter contains cis-acting element for the transcription factors Spl and E2F. Transcription of dhfr gene shows maximal activity during the Gl/S phase of cell cycle. The member of the Spl transcriptional factor family can act as both negative and positive regulators of gene expression. There was a report that Spl-Rb and E2F4-pl30 complexes cooperate to establish stable repression of dhfr gene expression in CHOC400 cells. Here, we examined the role of HDAC in dhfr, cyclin E, and cyclin A gene regulation using the histone deacetylation inhibitor, trichostatin A (TSA) in U2OS and C33A cells, a Rb-positive human osteosarcoma cell line, and a Rb-negative cervical carcinoma cell line, respectively. When the dhfr promoter constructs were applied in U2OS cells, TSA markedly stimulated over 14-fold of dhfr promoter activity through dhfr-Spl sites by the deletion of an E2F element. In contrast, the deletion of dhfr-Spl binding sites completely abolished promoter stimulation by TSA. The dhfr promoter activity including dhfr-Spl sites increased only 2-fold in C33A cells. Promoter activity containing only dhfr-E2F site did not have much effect by the treatment of TSA in both U2OS and C33A cells. On the other hand, treatment with TSA induced significantly mRNA expression of dhfr and cyclin E, whereas levels of cyclin A decreased in U2OS cells, but had no effect in C33A cells. These results indicate that TSA have contradictory effect, activation of dhfr and cyclin E genes on Gl phase, and down-regulation of cyclin A on G2 phase through transcriptional regulation in U2OS cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.2
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• pp.329-332
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• 2002

We investigated the effect of Sarcodon aspratus extract on expression of cell cycle regulators. Methanol extract of Sarcodon aspratus showed a growth suppression on HepG2. As shown by western blot analysis, the expressions of cyclin A and Dl known as cell cycle regulators were decreased after treatment of Sarcodon aspratus extract. On the other hand, the expression of cyclin Bl was increased in the presence of Sarcodon aspratus extract. Furthermore, the expression of p53, a tumor supressor gene, and p27, a cell cycle dependent protein kinase inhibitor, were increased, whereas the expression of PCNA was decreased. In conclusion, our study suggests that growth inhibitory effect of Sardodon aspratus methanol extract on HepG2 is induced by cell cycle arrest in the Gl phase caused by decrease in cyclin A, Dl expressions and increases in p53, p27 expression.