• 제목/요약/키워드: Cyclin A

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Downregulation of Cyclin D1 by Sophorae Flos through Proteasomal Degradation in Human Colorectal Cancer Cells

  • Lee, Jin Wook;Park, Gwang Hun;Eo, Hyun Ji;Jeong, Jin Boo
    • 한국자원식물학회지
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    • 제28권6호
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    • pp.727-733
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    • 2015
  • Although Sophorae Flos (SF) has been reported to exert an anti-cancer activity, molecular targets and mechanisms associated with anti-cancer activity of SF have been unclear. Because cyclin D1 has been regarded as an important regulator in the cell proliferation, we focused cyclin D1 and investigated the effect of SF on the cyclin D1 regulation in light of elucidating the molecular mechanism for SF’s anti-cancer activity. The treatment of SF decreased cellular accumulation of cyclin D1 protein. However, SF did not change the level of cyclin D1 mRNA. Inhibition of proteasomal degradation by MG132 attenuated SF-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with SF. In addition, a point mutation of threonine-286 to alanine attenuated SF-mediated cyclin D1 downregulation. Inhibition of ERK1/2 by a selective inhibitor, PD98059 suppressed cyclin D1 downregulation by SF. From these results, we suggest that SF-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2. SF-induced proteasomal degradation of cyclin D1 might inhibit proliferation in human colorectal cancer cells. The current study provides information on molecular events for an anti-cancer activity of SF

Cyclin A와 LATS 유전자들의 난소 내 mRNA 및 단백질 발현에 관한 연구 (Expression of mRNAs and Proteins of Cyclin A and LATS Genes in Ovary)

  • 박창은;김대중;홍성노
    • 대한임상검사과학회지
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    • 제40권1호
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    • pp.31-40
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    • 2008
  • Despite of the importance of the primordial follicle (PMF) recruitment, factors and mechanisms for process are poorly understood. To evaluate expression and role of the follicular transition from PMF to PMF/primary follicles (PMIF) in the present study, we evaluated expression of lats1, lats2, cyclin A1, and cyclin A2 mRNA and protein, and elucidated and role of lats1-cyclin A in the follicular transition from PMF to PRIF. To analysis of differential expression in PMF and PMIF, each stage follicles were collected by day1 and day5 of immuno-compromised rats (ICR) and analyzed by real-time PCR for the genes. For localization of mRNAs and proteins of the genes, in situ hybridization and immunohistochemistry were performed. We confirmed that the lats1, lats2, cyclin A1, and cyclin A2 mRNA were more expressed in PMF than PMIF. Localization of the four genes expression were observed in nuclei of oocytes from the arrested primordial, and in the surrounding granulosa cells of the growing follicles. The mRNA expressions were gradually decreased with follicular development. From immunohistochemistry studies, Cyclin A1 protein expression were observed in oocyte cytoplasmas of early stage follicles, while observed in granulose cells and oocyte nucleoli during growing follicles. This study suggested that the presence of lats gene family might perform negatively regulation of cell proliferation by modulation of the CDC2/Cyclin A complex activity. lats-cyclin A genes in oocytes of the early stage follicles might play a role in the meiotic cell cycle arrest of the primary oocytes at the primordial follicle stage as well as the follicular growth.

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완전 절제된 제IIIA기 비소세포폐암에서 Cyclin D1, p53, Bcl-2 단백질 발현의 의의 (Correlation between Cyclin D1, p53, Bcl-2 Protein Expression and Prognosis in Primary, Resected Stage IIIA Non-Small Cell Lung Cancer (NSCLC))

  • 정경영;양우익
    • Journal of Chest Surgery
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    • 제31권12호
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    • pp.1200-1205
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    • 1998
  • 연구목적: 폐암은 protooncogene의 활성화와 종양억제유전인자(tumor suppressor gene)의 비활성화 등 다단 과정에 의하여 발생한다. 치료목적의 완전 절제가 가능하였던 제 IIIA기 비소세포폐암 환자에서 cyclin D1, p53, bcl-2 gene의 변이가 폐암에 미치는 영향을 조사하고자 하였다. 대상 및 방법: 1990년부터 1995년까지 연세의료원에서 치료목적의 완전절제가 가능하였던 stageIIIA 비소세포폐암 환자 100명의 paraffin block과 임상기록을 이용하였다. 각 환자의 조직절편을 labelled streptavidin-biotin method로 immunohistochemical 염색하였고 cyclin D1, p53, Bcl-2 immunostaining을 위한 조직절편들은 immunostaining하기 전 citrate buffer 내에서 10분에서 20분간 microwave oven으로 전처치한 후 cyclin D1은 NCL-cyclin D1-GM으로 p53는 lone DO-7으로 bcl-2는 clone 124로 overnight incubation하였다. 수술 후 평균 추적조사기간은 24.1 개월(range; 2∼84 개월)이었다. 결과: 100예의 폐암 중 56예가 편평상피세포암, 37예가 선암, 5예가 adenosquamous cell carcinoma, 2예가 대세포암이었고 수술 후 5년 생존율은 32.1%이었다. cyclin D1의 양성율은 35 %, p53는 56 %, bcl-2는 17 %였으나 cyclin D1, p53, Bcl-2 단백질 양성 발현과 생존율과의 상관관계는 없었다. 결론: 연구결과 cyclin D1, p53, Bcl-2 단백질 양성 발현이 비소세포폐암 발생기전과 연관되어 있으나 수술 후 예후인자로서는 부적당한 것으로 판단되었다.

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구강 편평세포암종에서 Differential Polymerase Chain Reaction에 의한 Cyclin D1 유전자의 증폭에 대한 연구 (CYCLIN D1 GENE AMPLIFICATION IN ORAL SQUAMOUS CELL CARCINOMA USING DIFFERENTIAL POLYMERASE CHAIN REACTION)

  • 김기순;김경욱;이재훈;김창진
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제26권4호
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    • pp.355-362
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    • 2000
  • Neoplastic growth is characterized by alterations of oncogenes and antioncogenes. The interaction between activated oncogenes and functional deletion of antioncogene appears to be the driving force directing normal cells to uncontrolled growth resulting in tumor. In addition to those genes mentioned, other genes controlling the entry of cells into the cell cycle have recently been implicated in cancer development. The overexpression of the cyclin D1 gene, which has been mapped to 11q13, either by gene rearrangement or amplification has been noted in various malignant tumors. The product of the cyclin D1 gene forms a complex with cyclin-dependent protein kinases(CDK4) that governs a key transition in the cell cycle. The relationships between the overexpression of cyclin D1 assessed by immunihistochemistry and the amplification of the cyclin D1 gene by differential polymerase chain reaction(DPCR) using primers for dopamin D2 receptor gene in 13 cases of squamous cell carcinomas of the oral cavity have been studied. The semiquantitative assay of cyclin D1 amplification has been made by cyclin D1/dopamin D2 receptor(CD/DR) ratio. The results were as follows; 1. In the normal tissue and the tumor, the CD/DR ratios were 0.82 and 1.36 respectively. This implicates 1.65-fold amplification of cyclin D1 gene in tumor compared to that in normal tissue. 2. The tumor tissue which showed overexpression of cyclin D1 by immunohistochemistry revealed 2-fold amplification of cyclin D1 compared to the normal tissue. 3. The tumor tissue which showed mild expression of cyclin D1 by immunihistochemistry revealed 1.7-fold amplification of cyclin D compared to the normal tissue. 4. The cyclin D1 was overexpressed in the tumor tissue at the rate of 38%. Above results suggest that cyclin D1 has close correlation with the development of carcinoma in the oral cavity. But further studies were needed to elucidate the carcinogeneic mechanisms by comparative studies among cyclin D1, pRb and p53.

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위암조직에서 Cyclin G2 발현의 의의 (Cyclin G2 Expression in Gastric-cancer Tissues)

  • 최민규;홍성권;박승배;백용해;노재형;손태성;김성주;김성
    • Journal of Gastric Cancer
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    • 제5권4호
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    • pp.273-280
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    • 2005
  • 목적: cyclin G2는 여러 암종에서 세포 주기의 억제적 조절자로 알려져 있으나 위암에서의 발현 양상에 대해서는 거의 보고된 바가 없다. 본 연구에서는 위암에서 cyclin G2의 발현양상을 조사하고 이의 임상적 의의에 대해 알아보았다. 대상 및 방법: 1994년 11월부터 1997년 12월까지 위암으로 수술을 시행 받은 172명 환자의 암 조직에서 cyclin G2의 발현여부를 면역조직화학염색을 통해 조사하고 이에 따른 임상 및 병리학적 특성 비교 및 예후분석을 시행하였다. 결과: 전체 172개의 암조직 중 43예(25.0%)에서 cyclin G2의 발현이 양성이었다. cyclin G2 발현은 임상병기가 진행될수록 양성률이 더 낮게 나타났으며(P<0.001) 종양 침습 깊이가 더 진행된 경우와(P<0.05) 림프절 전이가 있거나(P<0.05) 림프관 침범이 있는 경우에 cyclin G2의 발현율이 낮았다.(P<0.05). 생존물의 비교 시 cyclin G2 양성군이 cyclin G2 음성군에 비해서 유의하게 예후가 좋았다(P<0.001). 다변량 분석 시 종양의 T 병기, 림프절 전이, 림프관 침범 여부가 독립적 예후인자로 유의하였으나 cyclin G2 발현여부는 유의하지 않았다. 결론: cyclin G2는 위암 조직의 25%에서 발현되었으며 이의 발현 음성은 보다 진행된 종양과 연관성이 있었다. cyclin G2는 위암의 증식에 억제 작용을 하는 것으로 생각되며 암 발생기전에 있어 이의 보다 정확한 역할에 대해 보다 많은 연구가 필요할 것으로 생각된다.

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G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

  • Zhang, Ying-Yao;Xu, Zhi-Na;Wang, Jun-Xi;Wei, Dong-Min;Pan, Xin-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권5호
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    • pp.2133-2137
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    • 2012
  • Objective: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). Methods: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. Results: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p = 0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). Conclusions: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection.

Induction of Cyclin D1 Proteasomal Degradation by Branch Extracts from Abeliophyllum distichum Nakai in Human Colorectal Cancer Cells

  • Park, Gwang Hun;Park, Jae Ho;Jeong, Jin Boo
    • 한국자원식물학회지
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    • 제28권6호
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    • pp.682-689
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    • 2015
  • Abeliophyllum distichum Nakai (A. distichum) has been reported to exert the inhibitory effect on angiotensin converting enzyme and aldose reductase. Recently, our group found that branch extracts of A. distichum (EAFAD-B) induce apoptosis through ATF3 activation in human colon cancer cells. However, anti-cancer reagents exert their activity through the regulation of various molecular targets. Therefore, the elucidation of potential mechanisms of EAFAD-B for anti-cancer activity may be necessary. To elucidate the potential mechanism of EAFAD-B for anti-cancer activity, we evaluated the regulation of cyclin D1 in human colon cancer cells. EAFAD-B decreased cellular accumulation of cyclin D1 protein. However, cyclin D1 mRNA was not changed by EAFAD-B. Inhibition of proteasomal degradation by MG132 attenuated EAFAD-B-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with EAFAD-B. In addition, EAFAD-B induced cyclin D1 phosphorylation at threonine-286 and the point mutation of threonine-286 to alanine attenuated EAFAD-B-mediated cyclin D1 proteasomal degradation. Inhibitions of both ERK1/2 by PD98059 and NF-κB by a selective inhibitor, BAY 11-7082 suppressed cyclin D1 downregulation by EAFAD-B. From these results, we suggest that EAFAD-B-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2-dependent NF-κB activation. The current study provides new mechanistic link between EAFAD-B and anti-cancer activity in human colon cancer cells.

Anti-Proliferative Activity of Ethanol Extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) Through Cyclin D1 Proteasomal Degradation in Human Colorectal Cancer Cells

  • Park, Gwang Hun;Song, Hun Min;Park, Su Bin;Park, Ji Hye;Shin, Myeong Su;Son, Ho-Jun;Um, Yurry;Jeong, Jin Boo
    • 한국자원식물학회지
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    • 제30권6호
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    • pp.640-646
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    • 2017
  • In this study, we elucidated anti-cancer activity and potential molecular mechanism of 70% ethanol extracts from Taxilli Ramulus (Taxillus chinensis (DC.) Danser) (TR-E70) against human colorectal cancer cells. Anti-cell proliferative effect of TR-E70 was evaluated by MTT assay. The effect of TR-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively. TR-E70 suppressed the proliferation of human colorectal cancer cell lines, HCT116 and SW480. Although TR-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by TR-E70 more dramatically occurred than that of cyclin D1 mRNA. Cyclin D1 downregulation by TR-E70 was attenuated in presence of MG132. In addition, TR-E70 phosphorylated threonine-286 (T286) of cyclin D1. TR-E70-mediated cyclin D1 degradation was blocked in presence of LiCl as an inhibitor $GSK3{\beta}$ but not PD98059 as an ERK1/2 inhibitor and SB203580 as a p38 inhibitor. Our results suggest that TR-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through $GSK3{\beta}$-dependent cyclin D1 degradation. From these findings, TR-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

독활 에탄올 추출물의 대장암 세포에서 Cyclin D1 단백질 분해 유도를 통한 세포 생육 억제활성 (Anti-proliferative Activity of Ethanol Extracts of Root of Aralia cordata var. continentalis through Proteasomal Degradation of Cyclin D1 in Human Colorectal Cancer Cells)

  • 박수빈;박광훈;송훈민;박지혜;신명수;손호준;엄유리;정진부
    • 한국약용작물학회지
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    • 제25권5호
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    • pp.328-334
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    • 2017
  • Background: In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the root of Aralia cordata var. continentalis (Kitagawa) Y. C. Chu (RAc-E70) against human colorectal cancer cells. Methods and Results: RAc-E70 suppressed the proliferation of the human colorectal cancer cell lines, HCT116 and SW480. Although RAc-E70 reduction cyclin D1 expression at the protein and mRNA levels, RAc-E70-induced reduction in cyclin D1 protein level occurred more dramatically than that of cyclin D1 mRNA. The RAc-E70-induced downregulation of cyclin D1 expression was attenuated in the presence of MG132. Additionally, RAc-E70 reduced HA-cyclin D1 levels in HCT116 cells transfected with HA-tagged wild type-cyclin D1 expression vector. RAc-E70-mediated cyclin D1 degradation was blocked in the presence of LiCl, a $GSK3{\beta}$ inhibitorbut, but not PD98059, an ERK1/2 inhibitor and SB203580, a p38 inhibitor. Furthermore, RAc-E70 phosphorylated cyclin D1 at threonine-286 (T286), and LiCl-induced $GSK3{\beta}$ inhibition reduced the RAc-E70-mediated phosphorylation of cyclin D1 at T286. Conclusions: Our results suggested that RAc-E70 may downregulate cyclin D1 expression as a potential anti-cancer target through $GSK3{\beta}$-dependent cyclin D1 degradation. Based on these findings, RAc-E70 maybe a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

Anticancer Activity of the Safflower Seeds (Carthamus tinctorius L.) through Inducing Cyclin D1 Proteasomal Degradation in Human Colorectal Cancer Cells

  • Park, Gwang Hun;Hong, Se Chul;Jeong, Jin Boo
    • 한국자원식물학회지
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    • 제29권3호
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    • pp.297-304
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    • 2016
  • The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.