• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.273-280
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• 2005

Purpose: Cyclin G2 has been reported to be a negative cell-cycle regulator in various cancer tissues. However, the pattern of cyclin G2 expression in gastric cancer is relatively unknown. We investigated the expression of cyclin G2 in gastric cancer tissues and evaluated the clinical significance of its expression. Materials and Methods: Well-preserved gastric cancer tissues were consecutively obtained from 172 patients who underwent gastric cancer operations at Samsung Medical Center between November 1994 and December 1997. Cyclin G2 expression in the tissues was examined immunohistochemically, and the clinicopathological features and prognostic significance according to the expression were analyzed. Results: Of the 172 gastric cancer tissues, cyclin G2 expression was positive in 43 tissues (25.0%). According to the stage, cyclin G2 expression was lower in more advanced stages (P<0.001). Negative expression of cyclin G2 was positively correlated with more advanced depth of tumor invasion (P<0.05), presence of lymph-node metastasis (P<0.05) and presence of lymphatic invasion (P<0.05). The prognosis of the cyclin G2(+) group was significantly better than that of the cyclin G2(-) group (P<0.001). Multivariate analysis revealed that T stage, lymph-node metastasis, distant metastasis, and lymphatic invasion were independent prognostic factors, but the expression of cyclin G2 was not. Conclusion: Cyclin G2 was expressed in 25% of the gastric cancer tissues, and negative expression of cyclin G2 was associated with more advanced tumor progression. Cyclin G2 may be a negative cell-cycle regulator in gastric cancer, and further studies are necessary to elucidate its exact role in the mechanism of carcinogenesis.

• BMB Reports
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• v.44 no.8
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• pp.553-557
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• 2011

We previously reported that CDK2/Cyclin A can phosphorylate and activate the transcription factor NF-Y. In this study, we investigated a potential regulatory role for NF-Y in the transcription of Cyclin A and other cell cycle regulatory genes. Gel-shift assays demonstrate that NF-Y binds to CCAAT sequences in the Cyclin A promoter, as well as to those in the promoters of cell cycle G2 regulators such as CDC2, Cyclin B and CDC25C. Furthermore, expression of Cyclin A increases NF-Y's affinity for CCAAT sequences in the CDC2 promoter; however, Cyclin A's induction of CDC2 transcription is antagonized by p21, an inhibitor of CDK2/Cyclin A. These results suggest a model wherein NF-Y binds to and activates transcription from the Cyclin A promoter, increasing cellular levels of Cyclin A/CDK2 and potentiating NF-Y's capacity for transcriptional transactivation, and imply a positive feedback loop between NF-Y and Cyclin A/CDK2. Our findings are additionally indicative of a role for Cyclin A in activating Cyclin B/CDK1 through promoting NF-Y dependent transcription of Cyclin B and CDC2; NF-Y mediated crosstalk may therefore help to orchestrate cell-cycle progression.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1425-1430
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• 2012

Cyclin L2 is a novel member of the cyclin family, recently implicated in the regulation of cell cycle progression and/or transcriptional regulation. The present study was undertaken to investigate the effects of overexpression on tumor cell growth and chemosensitivity in human gastric cells in vitro. Cyclin L2 was transfected into human gastric cancer cell line BCG823 and expressed with a mammalian expression vector pcDNA3.1. The effects and mechanisms of cyclin L2 on cell growth, cell cycling and apoptosis were studied. Compared to control vectors, overexpression of cyclin L2 inhibited the growth of BCG823 cells and enhance their chemosensitivity to fluorouracil, docetaxel and cisplatin. The anti-proliferative effects of cyclin L2 could be due to G0/G1 arrest and apoptosis. Cyclin L2 induced G0/G1 arrest and apoptosis involved upregulation of caspase-3 and down regulation Bcl-2 and survivin. The results indicated that overexpression of cyclin L2 protein may promote efficient growth inhibition and enhance chemosensitivity to chemotherapeutic agents in human gastric cancer cells by inducing G0/G1 cell cycle arrest and apoptosis.

• Environmental Mutagens and Carcinogens
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• v.24 no.1
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• pp.1-9
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• 2004

Three D-type cyelins (D1, D2, and D3) are expressed in G1 phase of the cell cyele and have been implicated in cell transformation and neoplasia in human and mouse. Cyclin D1 overexpression or amplification was described in various human cancers. However, there is controversy about the role of cyclin D2 in cell cyele progression and human carcinogenesis. Specially, loss of cyelin D2 is involved in a vital tumor suppressor function in normal breast tissue, and that its loss may be related to tumorigenesis. The author examined to effect over-expression of cyclin D2 on the cell proliferation, apoptosis, and cell cycle using cyclin D2 transfected stable T47D breast cancer cells to investigate whether cyclinD2 functions as a positive regulator or negative regulator in cell proliferation. Overexpression of cyclin D2 led to the suppression of cell growth in cyclin D2 transfected T47D in both in its expression level and a time dependent manner with up to 50% reduction of cell growth at 72 hours. Therefore, the authors performed the cell cycle phase analysis using the flow cytometry to investigate the effect of cyclin D2 on the cell cycle phase in cyclin D2 transfected stable T47D cells. The flow cytometry analysis revealed increased sub G0 phase in cyclin D2 transfeted cells up to 23% at 72 hours. To confirm these results induced by overexpression of cyclinD2, the apoptotic bodies were counted in control and cyclin D2 transfected T47 cells. There are markedly increases of apoptotic bodies in cyclin D2-transfected cells up to 18%. These results suggested that Cyclin D2 suppresses the cell proliferation in breast cancers cells via the induction of apotosis.

• Journal of Life Science
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• v.11 no.4
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• pp.362-370
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• 2001

Regulation of cell proliferation is a complex process involving the regulated expression and /or modification of discrete gene products. which control transition between different stages of the cycle. The purpose of this short review is to provide an overview of somatic cell cycle events and their controls. Cycline have appeared as major positive regulators in this network, because their association to the cyclin-dependent kinases(Cdks) allows the subsequent activation on the Cdk/cyclin complexes and their catalatic activity. In mammalian cells, early to mid G1 progression and late G1 progression leading to S phase entry are directed by D-type cyclins-Cdk4, 6 and cyclin E-Cdk 2 both of which can phosphorylate the retinoblastoma protein (pRB). pRB is a transcriptional repressor which, in its unphosphorylated state, binds to members of the E2F transcription factor family and blocks E2F-dependent transcription of genes controlling the G1 to S phase transition an subsequent DNA synthesis. Cyclin A is produced in late G1 and expressed during S and G2 phae, and expression of B-type cyclins is typically maximal during the G2 to M phase transition and it controls the passage through M phase. They primarily associate with the activate Cdk2, and Cdc2, respectively. On the other hand, the Cdk inhibitors negatively control the activity of C아/cyclin complex by coordinating internal and/or external signals and impending proliferation at several key checkpoints. These current and further findings will provide novel approaches to understanding and treating major diseases.

• 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.

• Animal cells and systems
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• v.9 no.4
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• pp.191-198
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• 2005

The effects of 6-aminonicotinamide (6-AN) on viability of IMR32 neuroblastoma cells in the presence of ATP or $NAD^+$ have been investigated. 6-AN caused marked reduction in cell viability and similar observations were also made with cells treated with 6-AN+ATP. However, cells treated with $6-AN+NAD^+$ showed cell viability similar to untreated cells. Morphologically, 6-AN and 6-AN+ATP treated cells showed loss of neurites, polyhedric shapes, shrinkage of cell bodies and formation of lysed cells, while $6-AN+NAD^+$ cells did not show any such changes. The flow cytometry analysis demonstrated that 6-AN increased cell population in $G_0/G_1$ phase and decreased cell population in Sand $G_2/M$ phase following a 72 h exposure. Western blot analysis showed that 6-AN stimulated a substantial increase in the level of the cdk inhibitor $p27^{kip1}$, but lowered the levels of cdk2, cyclin E and p-Rb. However, cdc25A and p53R2 were not significantly affected. Immunofluorscence staining of $p27^{kip1}$, cdk2, cyclin E and p-Rb revealed close correlation between the signal observed in the Western blot analysis. 6AN+ATP treated cells showed similar results obtained with 6-AN treated cells in expression of cdk2, cyclin E, p-Rb proteins and $p27^{kip1}$, $6-AN+NAD^+$ cells showed greater expression of cdk2, cyclin E and p-Rb than those in 6-AN and 6-AN+ATP treated cells. The results suggest that 6-AN induced the $G_0/G_1$ phase arrest in IMR32 neuroblastoma cell lines through the increase of $p27^{kip1}$ and the decrease of cdk2, cyclin E and p-Rb.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.6
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• pp.931-936
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• 2003

We investigated inhibitory effects of Hericium erinaceus on the growth of cancer cells and the expression of cell cycle regulators, cyclins. Anticancer effects of Hericium erinaceus extract and fractions against cancer cell lines including HepG2 and HT29 were investigated. The methanol extract, the hexane fraction, the chloroform fraction and the ethylacetate fraction of Hericiu erinacew inhibited growth of cancer cells but they had no effect on the cytotoxicity of normal human liver cells under the same conditions. As shown by western blot analysis, the expression of cyclin B1 known as cell cycle regulator was markedly decreased after treatment with Hericium erinaceus extract in HepG2 cells. These results suggest that antiproliferative effect of Hericaum erinaceus extract is associated with markedly decreased expression of cyclin B1.

• The Journal of the Korean bone and joint tumor society
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• v.14 no.2
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• pp.106-118
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• 2008

Purpose: Disturbed cell cycle regulatory proteins are key events underlying the development and/or progression of human malignancies. The aim of this study is to evaluate the protein expression status involved in G1/S cell cycle in human soft tissue sarcoma. Materials and Methods: We simultaneously evaluated the expression of Cyclin D1, Cyclin E, CDK4, CDK2, p16, p27, Rb, E2F1, p53 and Ki-67 by immunohistochemistry in 43 cases of soft tissue sarcoma Results: The Cyclin D1, Cyclin E, CDK4, CDK2, E2F1, and p53 were expressed in 25 (58.1%), 18 (41.9%), 13 (30.2%), 33 (76.7%), 20 (46.5%), and 18 cases (41.9%). The p16, p27, and Rb expressions were decreased in 26 (60.5%), 22 (51.2%) and 19 cases (44.2%). All of the cases showed alterations of more than one out of the above proteins. The increased Cyclin E expression and Ki-67 labeling index (LI) were significantly associated with histologic grade. The Cyclin E and E2F-1 expressions were increased in relapsed cases and the CDK4 expression was increased in cases of metastasis. Conclusion: Alterations of G1/S cell cycle regulatory proteins may play an important role in the tumoriogensis of soft tissue sarcomas. Our results suggest that increased expressions of Cyclin E, E2F1, and CDK4 were associated with tumor relapse or metastasis and could be considered as parameters of prognosis of soft tissue sarcoma.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.378-384
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• 1999

Retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP) induce the differentiation of the multipotent embryonic carcinoma cell line, F9 cells, into parietal endoderm like cell. The F9 cells are highly proliferative doubling approximately 12 hourse. S Phase is predominant, lasting 10 hours and G2/M phase occupies most of the remaining cycle (2 hours) and G1 phase is nearly non-existent. In this study, we showed the effect of RA and dbcAMPon the cell cycle associated molecules (especially around G1 phase) during F9 cell differentiation. Differentiation of F9 cells was induced by the combined addition of RA ($10^{-7}M$) and dbcAMP (0.5mM), and cells were harvested daily up to 4 days. Flow cytometric analysis showed the prolongation of G1 phase around 30 hours after induction. Western blot analysis revealed that the amount of cyclin D1 and cdk2 were increased at day 4. However, histone H1 kinase activity of cdk2 was decreased. These data strongly suggest that RA and dbcAMP induce the growth arrest of F9 cells at G1 phase by decreasing the activity of cdk2, although they have increased the protein contents of cyclin D1 and cdk2. The reason for the discrepancy between the H1 kinase activity and protein contents are not clear yet.