• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제43권5호
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• pp.324-330
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• 2017

Objectives: There are only a limited number of studies on cyclin D1 and p63 expression in oral squamous cell carcinoma (OSCC) and leukoplakia. This study compared cyclin D1 and p63 expression in leukoplakia and OSCC to investigate the possible correlation of both markers with grade of dysplasia and histological grade of OSCC. Materials and Methods: The study included a total of 60 cases, of which 30 were diagnosed with OSCC and 30 with leukoplakia, that were evaluated immunohistochemically for p63 and cyclin D1 expression. Protein expression was correlated based on grades of dysplasia and OSCC. Results: Out of 30 cases of OSCC, 23 cases (76.7%) were cyclin D1 positive and 30 cases (100%) were p63 positive. Out of 30 cases of leukoplakia, 21 cases (70.0%) were cyclin D1 positive and 30 (100%) were p63 positive (P<0.05). Conclusion: The overall expression of cyclin D1 and p63 correlated with tumor differentiation, and increases were correlated with poor histological grades, from well-differentiated to poorly-differentiated SCC. Increased cyclin D1 and p63 expression was associated with the severity of leukoplakia. Based on these results cyclin D1 and p63 products can be a useful tool for improved leukoplakia prognosis.

• 생명과학회지
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• 제25권10호
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• pp.1184-1195
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• 2015

새로운 실험 동물로 대두되고 있는 제브라피쉬는 척추동물 생식생물학 연구에서도 중요한 역할을 한다. 제브라피쉬의 난자 성숙은 maturation inducing hormone (MIH, 17α,20β-Dihydroxy-4-pregnen-3-one)에 의해 촉발된다. 대부분의 동물의 난자성숙에는 cdc2 kinase와 cyclinB 단백질 복합체인 MPF의 활성화가 필요하다. 발톱개구리와 생쥐에서는 MPF 활성이 두 가지 기작에 의해 조절되는데, 하나는 cyclinB 결합이고 또 다른 하나는 Wee1과 Cdc25에 의한 T14/Y15 잔기의 억제성인산화와 탈인산화이다. 발톱개구리나 생쥐와 달리 제브라피쉬를 포함한 대부분의 진골어류(teleost)는 GV 난자에 pre-MPF complex가 존재하지 않으므로 MPF 활성화는 전적으로 cyclinB 단백질의 de novo synthesis에 의존한다. 다른 종과 마찬가지로 제브라피쉬의 모계유래 mRNA도 CPEB, Dazl, Pum1/Pum2, insulin-like growth factor2 mRNA-binding protein 3 등 다양한 RNA binding protein (RBP)의 결합에 의해 번역이 조절된다. 그러나 제브라피쉬 난자에서 단백질 번역 조절에 관여하는 자세한 작용 기작은 확실하게 규명되지 않았다. 그러므로 제브라피쉬 난자의 성숙과정을 연구하는 것은 척추동물 난자 초기 성숙과정에서 단백질 번역 조절의 역할을 규명할 수 있는 새로운 정보를 제공할 것이다.

• 생명과학회지
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• 제16권4호
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• pp.589-597
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• 2006

본 연구에서는 T24 인체방광암 및 U937 백혈병 세포의 증식에 미치는 genistein의 영향을 조사 하였다. Genistein이 처리된 T24 및 U937 세포는 처리 농도 의존적으로 세포의 증식이 현저히 감소되었으며 심한 형태적 변형이 동반되었으나, U937 세포에서 보다 높은 감수성을 보였다. 이러한 T24 및 U937 세포의 증식억제 및 형태 변형은 G2/M기의 세포주기 억제 및 apoptosis 유발과 연관성이 있음을 flow cytometry를 이용한 세포주기의 분석을 통하여 확인하였다. T24 세포에서 genistein에 의한 G2/M arrest는 cyclin A, cyclin B1 및 Cdc25C 등의 단백질 발현 감소와 연관성이 있었으나, 종양억제 유전자 p53 및 Cdk inhibitor p21의 발현에는 큰 변화가 없었다. U937 세포에서 genistein에 의한 G2/M arrest는 cyclin B1 및 p53 비의존적인 p21의 발현 증가와 연관성이 있었다. 이상의 결과들은 현재까지 거의 연구가 진행된 바 없는 인체방광암 및 백혈병 세포에서 genistein의 항암작용을 이해하는데 중요한 자료가 될 것이고 나아가 genistein을 포함한 그와 유사한 항암제 후보물질들의 연구에 있어서 기초 자료로서 사용될 수 있을 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4101-4107
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• 2014

Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls gene expression and cell cycle progression. The active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for PP1, has been shown to inhibit the growth of human cervix carcinoma cells (HeLa). In order to elucidate the underlying mechanisms, the present study assessed overexpression of $8-60hIPP5^m$ in HeLa cells. Flow cytometric and biochemical analyses showed that overexpression of $8-60hIPP5^m$ induced G2/M-phase arrest, which was accompanied by the upregulation of cyclin B1 and phosphorylation of G2/M-phase proteins ATM, p53, $p21^{cip1/waf1}$ and Cdc2, suggesting that $8-60hIPP5^m$ induces G2/M arrest through activation of the ATM/p53/$p21^{cip1/waf1}$/Cdc2/cyclin B1 pathways. We further showed that overexpression of $8-60hIPP5^m$ led to delayed nuclear translocation of cyclin B1. $8-60hIPP5^m$ also could translocate to the nucleus in G2/M phase and interact with $pp1{\alpha}$ and Cdc2 as demonstrated by co-precipitation assay. Taken together, our data demonstrate a novel role for $8-60hIPP5^m$ in regulation of cell cycle in HeLa cells, possibly contributing to the development of new therapeutic strategies for cervix carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6437-6441
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• 2014

Background: Oridonin isolated from Rabdosia rubescens, a plant used to treat cancer in Chinese folk medicine, is one of the most important antitumor active ingredients. Previous studies have shown that oridonin has antitumor activities in vivo and in vitro, but little is known about cell cycle effects of oridonin in gastric cancer. Materials and Methods: MTT assay was adopted to detect the proliferation inhibition of SGC-7901 cells, the cell cycle was assessed by flow cytometry and protein expression by Western blotting. Results: Oridonin could inhibit SGC-7901 cell proliferation, the $IC_{50}$ being $15.6{\mu}M$, and blocked SGC-7901 cell cycling in the $G_2/M$ phase. The agent also decreased the protein expression of cyclinB1 and CDK1. Conclusions: Oridonin may inhibit SGC-7901 growth and block the cells in the $G_2/M$ phase by decreasing Cdk1 and cyclinB1 proteins.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 전기 한국발생생물학회 제16차 학술대회논문집
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• pp.21-23
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• 2003

Mechanisms regulate the arrest and growth of the resting primordial follicles are very poorly understood. To elucidate genes involved in the early folliculogenesis, we conducted suppression subtractive hybridization using mRNA from day1 and day5 ovaries and selected weel for further analysis, since it was most frequent gene in the day1-subtracted cDNA library (1). Expression of weel and correlated components of the cell cycle machinery, such as cdc2, cyclin B1, cdc25C, and phosphorylated cdc2 was evaluated by immunohistochemistry. In primordial follicles, expression of weel, cdcw, and cyclin B1 was cytoplasmic in oocytes, but phosphorylated cdc2 was weakly expressed in oocytes. While cdc25C expression was in ovarian somatic and in some theca cells. None of components was expressed in the pre-granulosa cells of the primordial follicles, while weel weakly, and cdc2 and cyclin B1 was strongly expressed in the granulosa cells of the growing follicles. Results from the present study suggest that 1) the mejotic arrest of the oocytes may not due to of cell cycle machinery, and 2) the weel may arrest meiosis by sequestering cdc2 and cyclin B1 in the cytoplasm by protein-protein interactions and/or by inhibitory phosphorylation.

• Molecules and Cells
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• 제39권9호
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• pp.699-704
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• 2016

Developmentally regulated GTP-binding protein 2 (DRG2) plays an important role in cell growth. Here we explored the linkage between DRG2 and G2/M phase checkpoint function in cell cycle progression. We observed that knockdown of DRG2 in HeLa cells affected growth in a wound-healing assay, and tumorigenicity in nude mice xenografts. Flow cytometry assays and [$^3H$] incorporation assays indicated that G2/M phase arrest was responsible for the decreased proliferation of these cells. Knockdown of DRG2 elicited down-regulation of the major mitotic promoting factor, the cyclin B1/Cdk1 complex, but upregulation of the cell cycle arresting proteins, Wee1, Myt1, and p21. These findings identify a novel role of DRG2 in G2/M progression.

• 생명과학회지
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• 제23권6호
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• pp.832-837
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• 2013

본 연구에서는 생체 내 구성요소 및 에너지원으로서 중요한 역할을 하는 글루타민 결핍에 의한 인체 전립선 PC3 암세포의 증식에 관한 기전 연구를 실시하였다. 글루타민 결핍에 의한 PC3 세포의 증식억제는 세포주기 G2/M arrest와 연관성이 있었으나, apoptosis 유발 현상은 관찰되지 않았다. 글루타민 결핍에 의한 G2/M arrest는 전사 및 번역 수준에서 Cdc2, cyclin A 및 cyclin B1의 발현 억제 및 p53 비의존적인 p21(WAF1/CIP1)의 발현 증가와 연관성이 있었다. 아울러 글루타민 결핍은 Chk1 및 Chk2의 인산화를 증가시켰으나, Cdc25C의 인산화는 감소시켰다. 본 연구의 결과는 글루타민 결핍에 의한 PC3 세포의 증식억제가 apoptosis 유발과는 상관없이 G2/M arrest를 유발시킨다는 첫 번째 증거이다.

• 생명과학회지
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• 제11권4호
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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.

• Toxicological Research
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• 제20권1호
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• pp.71-82
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• 2004

Changes in cell cycle control in the lungs and liver of the B6C3F1 mice (20 males per each group) exposed to ozone (0.5 ppm), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1.0 mg/kg), and dibutyl phthalate (DBP, 5,000 ppm) after 52 weeks were examined through Western, Northern blot, and immunohistochemistry based on alterations in protein expression levels of G1/S checkpoints (cyclin D1, cyclin E, and PCNA), G2/M checkpoints (cyclin B1, cyclin G, and cyclin A), negative regulators (p53, p21, GADD45, and p27), and positive regulator (mdm2). Expression levels of cyclins D1, E, G, PCNA, mutant p53, and mdm2 proteins were higher in the lungs and livers treated with combination of toxicants than in those treated with ozone only. Expression levels of the wild-type and mutant p53, p21, GADD45, p27, and mdm2 proteins and mRNAs were higher in toxicant-treated groups than those of the control. Immunohistochemical analysis revealed staining intensities of the PCNA, cyclin D1, c-myc and mdm2 protein- treated lungs and livers were stronger than those of the control group. Our results showed that combined treatment of ozone with NNK/DBP altered the cell cycle control through instability of the wild-type p53 gene. Such pivotal p53-mediated cell cycle alterations may be responsible for the toxicity observed under our experimental condition. These results may be applied to risk assessment of mixture-induced toxicity.