• Title/Summary/Keyword: MYC2

검색결과 173건 처리시간 0.028초

Roles of Transcription Factor Binding Sites in the D-raf Promoter Region

  • Kwon, Eun-Jeong;Kim, Hyeong-In;Kim, In-Ju
    • Animal cells and systems
    • /
    • 제2권1호
    • /
    • pp.117-122
    • /
    • 1998
  • D-raf, a Drosophila homolog of the human c-raf-1, is known as a signal transducer in cell proliferation and differentiation. A previous study found that the D-raf gene expression is regulated by the DNA replication-related element (DRE)/DRE-binding factor (DREF) system. In this study, we found the sequences homologous to transcription factor C/EBP, MyoD, STAT and Myc recognition sites in the D-raf promoter. We have generated various base substitutional mutations in these recognition sites and subsequently examined their effects on D-raf promoter activity through transient CAT assays in Kc cells with reporter plasmids p5'-878DrafCAT carrying the mutations in these binding sites. Through gel mobility shift assay using nuclear extracts of Kc cells, we detected factors binding to these recognition sites. Our results show that transcription factor C/EBP, STAT and Myc binding sites in D-raf promoter region play a positive role in transcriptional regulation of the D-raf gene and the Myo D binding site plays a negative role.

  • PDF

항암활성물질을 생산하는 토양방선균의 동정 및 함암물질의 생물학적 활성 (Identification of Soil Actinomycetes Producing Anticancer Agent and Its Biological Activities)

  • 박정민;문순옥;오두환
    • 한국미생물·생명공학회지
    • /
    • 제22권4호
    • /
    • pp.347-352
    • /
    • 1994
  • Cytotoxic test was performed by SRB assay on human epidermoid carcinoma HEp-2 cell line for screening the soil microorganism, secreting anticancer agent. One microorganism was selected among two thousand microorganisms for its highest cytotoxicity. And this microorganism was identified with Streptomyces species after performing of diaminopimeric acid and reducing sugar analysis of cell wall and analysing the cultural characteristics and named Streptomyces sp. SM 1119. The effect of anticancer agent in SM 1119 culture extract on the cell cycle was studied by using GG$_{o}$ synchronized NIH 3T3 cells. The extract inhibited the serum stimulation of GG$_{o}$ NIH 3T3 cell only within 1 hour after serum stimulation but not after 6 hours. The extract also reduced the amount of c-myc mRNA in Colo 320 cell. These results suggest that the anticancer agent in the extract inhibits the progression of cell cycle very early stages, probably from G$_{0}$ to G$_{1}$.

  • PDF

Stemness and Proliferation of Murine Skin-Derived Precursor Cells under Hypoxic Environment

  • Kim, Hyewon;Park, Sangkyu;Roh, Sangho
    • International Journal of Oral Biology
    • /
    • 제41권2호
    • /
    • pp.69-74
    • /
    • 2016
  • Skin-derived precursors (SKPs) have potential to differentiate to various cell types including osteoblasts, adipocytes and neurons. SKPs are a candidate for cell-based therapy since they are easily accessible and have multipotency. Most mammalian cells are exposed to a low oxygen environment with 1 to 5% $O_2$ concentration in vivo, while 21% $O_2$ concentration is common in in vitro culture. The difference between in vitro and in vivo $O_2$ concentration may affect to the behavior of cultured cells. In this report, we investigated the effect of hypoxic condition on stemness and proliferation of SKPs. The results indicated that SKPs exposed to hypoxic condition for 5 days showed no change in proliferation. In terms of mRNA expression, hypoxia maintained expression of stemness markers; whereas, oncogenes, such as Klf4 and c-Myc, were downregulated, and the expression of Nestin, related to cancer migration, was also downregulated. Thus, SKPs cultured in hypoxia may reduce the risk of cancer in SKP cell-based therapy.

인동등(忍冬藤)이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향 (Effects of Lonicerae Caulis (LC) on Gene Expression of Human melanoma cells)

  • 김대수;최정화;김종한;박수연;강성인
    • 한방안이비인후피부과학회지
    • /
    • 제22권1호
    • /
    • pp.11-32
    • /
    • 2009
  • Objective : This study was designed to investigate anti-cancer and whitening activities (LC). So it was investigated the effects of LC on proliferation rates of melanoma genetic profile by LC. Methods : The genetic profile for the effect of LC on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes were conducted. Total 441 genes were up-regulated and 830 genes down-regulated in cells treated with LC. Genes induced or suppressed by LC were all mainly concerned with basic signalling pathways, which are involved in cell growth, differentiation and migration. Especially, many genes, which are related in apoptosis and cell cycle arrest were up-regulated by treatment with LC, and genes related in cell cycle were down-regulated. Result : The network of total protein interactions were identified by using cytoscape program, and some key molecules, such as BCL2L1, SIN3A, SMAD2 and c-myc that can be used for elucidation of therapeutical mechanism of medicine in the future. Conclusion : These results suggest possibility of LC as addition drug and whitening cosmetics. In addition, it was also suggested that related mechanisms are involved in BCL2L1, SIN3A, SMAD2 and c-myc related signalling pathways.

  • PDF

RNases and their role in Cancer

  • Beeram, Eswari
    • 식품보건융합연구
    • /
    • 제5권2호
    • /
    • pp.27-34
    • /
    • 2019
  • RNases plays a pivotal role in biological system and different RNases are known for their various functions like angiogenesis, immunological response, antiviral, antitumour activity and apoptosis. In which anti tumour activity of RNase is proved to improve genome stability in normal cells up to some extent. RNases like RNase L shows antiviral and antitumour activities against virus infected cells and cancer cells through 2'-5' oligo adenylate pathway and induces RNaseL dependent apoptosis where as RNase A modulates various proliferative pathways like MAP kinase, JNK, TGF-${\beta}$ and activates apoptosis in cancer cells and promotes immunological response through processing of Ags. IRE1 RNase acts as both tumour suppressor gene and oncogene in normal and cancer cells and involved in both antitumour and tumorigenic activities. RNase III upregulates miRNA in cancer cells there by acting via posttranscriptional level and proven to be effective against colorectal adeno carcinoma. In addition to this IRE1 RNase is a double edged sword through RIDD pathway in ER (18). To some of the cancers expressing c-myc IRE1 acts as tumour suppressor where as in cancers where myc is downregulated IRE1 acts as tumour provoking through RIDD pathway (18). Thus RNases play vital role in regulating the genome stability.

페리틴 리포터 유전자를 발현하는 백서 중간엽 줄기세포의 특성과 자기공명영상 연구 ($In$ $vitro$ MRI and Characterization of Rat Mesenchymal Stem Cells Transduced with Ferritin as MR Reporter Gene)

  • 신청일;이활;우지수;박은아;김판기;송현복;김회숙
    • Investigative Magnetic Resonance Imaging
    • /
    • 제16권1호
    • /
    • pp.47-54
    • /
    • 2012
  • 목적: 백서 중간엽 줄기세포에 페리틴 유전자를 형질 도입시켜 생물학적 특성의 변화 유무를 평가하고, 자기공명영상에서 신호강도의 차이를 확인해보고자 하였다. 대상과 방법: 백서 중간엽 줄기세포에 렌티바이러스를 이용하여 사람유래 재조합 페리틴과 녹색형광단백질 유전자의 과발현을 유도하였다. 페리틴 유전자가 발현된 백서 중간엽 줄기세포의 증식성과 생존능을 분석하기 위해 MTT 어세이를 수행하였으며, 유세포 분석을 수행하여 중간엽 줄기세포의 표면 마커 발현을 평가하고, 세포 내 철 함량을 측정하고 프러시안 블루 염색을 시행하여 철 축적능력을 분석하였다. 세포 팬텀을 이용하여 9.4 T 자기공영영상 기기를 이용하여 검출가능성을 평가하였다. 결과: 페리틴과 녹색형광 유전자는 백서 중간엽 줄기세포에서 안정적으로 발현되었다. 페리틴 유전자의 과발현으로 인해 백서 중간엽 줄기세포의 생물학적 특성 (증식능력, 생존능, 표면마커)은 영향을 받지 않았다. 페리틴을 발현하는 중간엽 줄기세포에서 철의 축적능력이 증가된 것이 확인되었고, T2 이완 시간은 유의하게 감소하였다. 결론: 줄기세포 치료 연구에서 자기공명 리포터 유전자 페리틴은 자기공명영상법을 이용하여 중간엽 줄기세포를 비침습적으로 가시화 할 수 있고 이를 이용하여 생체추적이 가능할 것으로 기대된다.

High expression of RAD51 promotes DNA damage repair and survival in KRAS-mutant lung cancer cells

  • Hu, Jinfang;Zhang, Zhiguo;Zhao, Lei;Li, Li;Zuo, Wei;Han, Lei
    • BMB Reports
    • /
    • 제52권2호
    • /
    • pp.151-156
    • /
    • 2019
  • RAD51 recombinase plays a critical role in homologous recombination and DNA damage repair. Here we showed that expression of RAD51 is frequently upregulated in lung cancer tumors compared with normal tissues and is associated with poor survival (hazard ratio (HR) = 2, P = 0.0009). Systematic investigation of lung cancer cell lines revealed higher expression of RAD51 in KRAS mutant (MT) cells compared to wildtype (WT) cells. We further showed that MT KRAS, but not WT KRAS, played a critical role in RAD51 overexpression via MYC. Moreover, our results revealed that KRAS MT cells are highly dependent on RAD51 for survival and depletion of RAD51 resulted in enhanced DNA double strand breaks, defective colony formation and cell death. Together, our results suggest that mutant KRAS promotes RAD51 expression to enhance DNA damage repair and lung cancer cell survival, suggesting that RAD51 may be an effective therapeutic target to overcome chemo/radioresistance in KRAS mutant cancers.

비소세포 폐암에서의 Microsatellite Instability와 p53. K-ras, c-myc 암단백의 발현 (Microsatellite Instability and p53, k-ras c-myc Oncoprotein Expression in Non-Small Cell Lung Carcinoma)

  • 나석주;곽문섭
    • Journal of Chest Surgery
    • /
    • 제33권1호
    • /
    • pp.60-67
    • /
    • 2000
  • Background: Microsatellites are short-tandem repeated uncleotide sequences present throughout the human genome. Alterations of microsatellites have been termed microsatellite instability(MI). It has been generally known that microsatellite instability detected in hereditary non-polyposis colorectal cancer (HNPCC) reflects genetic instability that is caused by impairments of DNA mismatch repair system regarding as a novel tumorigenic mechanism. A number of studies reported that MI occurred at varying frequencies in non-small cell lung carcinoma (NSCLC). However It has been unproven whether MI could be a useful market of genetic instability and have a clinical significance in NSCLC. Material and Method : We have examined whether MI can be observed in thirty NCSLC using polymerase chain reaction whether such alterations are associated with other molecular changes such as p53, K-ras and c-myc oncoproteins expression detected by immunohistochemical stain,. Result: MI(+) was observed in 16.6%(5/30) and MI(-) was 83.3% (25/30) Average age was 50$\pm$7.5 year-old in MI(+) group and 57$\pm$6.6 year-old in MI(-) group. Two year survival rate in MI(=) group (20% 1/5) was worse than MI(-) group (64% 16/25) with a statistic difference. (P=0.04) The positive rate of K-ras oncoprotein expression and simultaneous expression of 2 or 3 oncoproteins expression were higher in MI(+) group than MI(-) group with a statistic difference(P=0.05, P=0.01) Conclusion: From, these results the authors can conclude that MI is found in some NSCLC and it may be a novel tumorigenic mechanism in some NSCLC. We also conclude that MI could be used as another poor prognostic factor in NSCLS.

  • PDF

하인두암에서의 N-myc Downstream Regulated Gene-1 발현의 임상적 의의 (Expression and Clinical Significance of the N-myc Downstream Regulated Gene-1 in Hypopharyngeal Cancer)

  • 손인경;한남수;신유섭;김장희;김철호
    • 대한두경부종양학회지
    • /
    • 제27권1호
    • /
    • pp.22-26
    • /
    • 2011
  • 목 적 : 두경부 암은 발생 순위에서 전체 6위에 해당하는 다빈도 암이나 최근 20여년 동안의 노력에도 불구하고 두경부 암의 독톡한 특성상 생존률에서 뚜렷한 향상을 보이지 못하고 있다. 특히, 하인두 암은 원발 부위의 점막하 침윤이 흔하며, 주변 림프절 전이와 원격 전이가 흔하고, 2차 원발 암종 발생이 흔하여 두경부 암 중에서도 가장 불량한 예후를 보이고 있는 악성 종양이다. 최근에 이러한 암을 치료하고 진단하기 위한 방법으로 분자생물학적 접근법들이 많이 시도 되고 있으며, 그 중 하나로 N-myc downstream regulated gene-1(Ndrg-1)이라는 유전자가 유방, 전립선, 방광 암 등의 타 악성 종양에서 종양의 전이 및 진행 양상과 관련되어 있다는 보고가 있었다. 이에 본 연구는 하인두 암에서의 Ndrg-1의 발현 양상을 살펴보고 이와 임상 양상과의 연관관계를 살펴보고자 하였다. 방 법 : 1996년부터 2003년까지 수술 받은 하인두 암 환자 56명을 대상으로 면역조직화학검사를 시행하여 Ndrg-1 발현을 확인하였고, 3명의 신선 조직을 대상으로 RT-PCR, Western blot을 시행하였다. 결 과 : Ndrg-1은 RT-PCR에서 정상 조직과 악성종양 조직 모두에서 비슷한 수준으로 발현되었다. 그러나 Western blot에서는 정상 조직에서 뚜렷한 증가 양상을 보여 타 연구와 동일한 결과를 보였고, 이는 불필요하며 비효율적인 mRNA수준에서의 발현이 있지만 최종적인 단백 산물 발현에서는 암종의 진행과 연계되어 악성 종양 진행군에서 발현이 억제되는 결과로 해석된다. 면역조직화학검사에서는 정상 상피조직에서 Ndrg-1 발현이 확인되었으며, 통계적으로 유의하지는 않으나 불량한 예후를 가진 그룹에서 대체로 발현이 억제되는 악성 종양과의 역 연관 관계를 확인할 수 있었고, 특히 림프절 전이를 보인 그룹과 그렇지 않은 그룹 사이에서는 통계적으로 유의미한 결과가 확인되었다. 결 론 : 즉, 림프절 전이가 없는 그룹에서 Ndrg-1이 종양의 전이에 관여할 것이라는 타 연구와 일관된 결과로 하인두 암에서도 그 역할이 있음을 나타내는 결과라 할 수 있다.