• 제목/요약/키워드: p53gene

검색결과 618건 처리시간 0.034초

Cadmium Toxicity Monitoring Using Stress Related Gene Expressions in Caenorhabditis elegans

  • Roh, Ji-Yeon;Park, Sun-Young;Choi, Jin-Hee
    • Molecular & Cellular Toxicology
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    • 제2권1호
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    • pp.54-59
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    • 2006
  • The toxicity of cadmium on Caenorhabditis elegans was investigated to identify sensitive biomarkers for environmental monitoring and risk assessment. Stress-related gene expression were estimated as toxic endpoints Cadmium exposure led to an increase in the expression of most of the genes tested. The degree of increase was more significant in heat shock protein-16.1, metallothionein-2, cytochrome p450 family protein 35A2, glutathione S-transferase-4, superoxide dismutase-1, catalase-2, C. elegans p53-like protein-1, and apoptosis enhancer-1 than in other genes. The overall results indicate that the stress-related gene expressions of C. elegans have considerable potential as sensitive biomarkers for cadmium toxicity monitoring and risk assessment.

EGCG, genistein, resveratrol 처리에 의한 ATF3와 NAG-1 유전자 발현변화의 p53 의존성 분석 (Dependency on p53 in Expression Changes of ATF3 and NAG-1 Induced by EGCG, Genistein, and Resveratrol)

  • 김민정;김현지;서유미;이은주;김종식
    • 생명과학회지
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    • 제28권5호
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    • pp.615-620
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    • 2018
  • EGCG는 녹차의 카테킨 중의 하나로서 항산화, 항염증 그리고 항암 활성 등 다양한 생리활성을 가지고 있는 물질로 알려져 있다. 본 연구에서는 EGCG를 처리한 HCT116 세포와 p53-null HCT116 세포에서 oligo DNA microarray 실험을 통하여 유전자 발현 변화를 분석하였다. Microarray 실험에서 EGCG를 처리한 HCT116 세포주에서 증가된 유전자 4개(ATF3, CDKN1A, DDIT3, NAG-1)를 선별하여, p53-null HCT116에서의 데이터와 비교하였다. NAG-1을 제외한 3개의 유전자는 p53의 상태와 관계없이 발현이 증가하였고, p53-null HCT116 세포주에서는 EGCG에 의해 NAG-1의 발현이 증가되지 않았다. EGCG의 처리에 의해 ATF3와 NAG-1의 유전자와 단백질의 발현을 확인한 경우 동일한 결과를 보여주었다. 또한, 파이토케미칼 genistein과 resveratrol을 처리한 후 ATF3와 NAG-1의 발현을 연구한 결과 genistein은 p53의 상태와 관계없이 ATF3 발현에 영향을 주지 못하는 반면, NAG-1 단백질은 p53 존재 하에서만 발현이 증가되었다. 이에 반해 resveratrol은 p53의 상태와는 관계없이 ATF3와 NAG-1 단백질의 발현을 증가시켰다. 따라서, 항암 활성을 가진 3 종류의 파이토케미칼이 각각 다른 기전으로 항암 유전자를 발현시키는 것으로 생각된다. 종합적으로 본 연구결과는 파이토케미칼 EGCG, genistein, resveratrol에 의해 매개되는 항암 활성의 기전을 이해하는데 도움을 줄 것으로 생각된다.

기관지도말 표본에서 p53단백 발현의 진단적 의의 (Diagnostic Application of p53 IMMUNOSTAINING in Bronchial Brush Specimens)

  • 이상숙;배지연;강유나;조영록;김시남;박남조;김선영;김정희
    • 대한세포병리학회지
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    • 제7권2호
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    • pp.163-168
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    • 1996
  • Abnormalities of p53 gene are common in lung cancers and are associated with immunologically detectable p53 protein. p53 immunoreactivity is uncommon in normal cells but is frequently seen in neoplasia. Therefore, assessment of p53 expression may assist in the cytological diagnosis of malignancy. The usefulness of p53 immunostaining as a marker of malignancy in the cytological analysis of bronchial brush specimens from the patients with lung cancers was investigated in this study. A total of 71 bronchial brush samples submitted for cytologic diagnosis were immunostained with D07, a monoclonal antibody to recombinant p53 protein. Resultant p53 data were correlated with cytologic diagnosis and clinical information. Of the 17 smears with a benign cytodiagnosis, all were p53 negative. Of the 40 cases with a malignant cytodiagnosis (histologically confirmed), 35 were p53 positive and 5 were negative. Of the 14 cases that were cytologically suspicious but nondiagnostic for malignancy, 11 were p53 positive, 9 of which were subsequently proved to be malignant by histologic examination, and the remaining 2 cases were tuberculosis clinically. Forty four of 51 histologically confirmed lung carcinomas were p53 positive, including 25 of 28 squamous cell carcinomas, 13 of 17 small cell carcinomas, 3 of 3 adenocarcinomas, and 3 of 3 large cell undifferentiated carcinomas. These results suggest that p53 immunostaining could be of value as a marker of malignancy in the cytologic examination of bronchial brush specimens. Furthermore, we have shown the possible clinical utility of p53 immunostaining in cytopathological diagnosis, that is, as a valuable adjunct to morphological assessment in the analysis of cytopathologically suspicious cases.

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P53 Polymorphism at Codon 72 is Associated with Keratocystic Odontogenic Tumors in the Thai Population

  • Yanatatsaneejit, Pattamawadee;Boonsrang, Ajaree;Mutirangura, Apiwat;Patel, Vyomesh;Kitkumthorn, Nakarin
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권5호
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    • pp.1997-2001
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    • 2015
  • Objective: To clarify the association between the p53 polymorphism at codon 72 and susceptibility to the sporadic keratocystic odontogenic tumor (KCOT). Design: One hundred KCOTs and 160 match-group healthy controls were genotyped to ascertain the frequency of the p53 codon 72 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), confirmed by direct sequencing. Results: The frequencies of the Pro/Pro, Arg/Pro, and Arg/Arg genotypes were 23.8%, 49.4%, and 26.9%, respectively, in the controls, while the KCOT cohort demonstrated 43.0%, 39.0%, and 18.0%, respectively. Further analysis suggested that p53 Pro could be a KCOT-susceptible allele (OR (95%CI)=1.77 (1.22 to 2.59), p=0.0024), with a sex-adjusted OR (95%CI) of 1.71 (1.17-2.50), p=0.0046. Moreover, the results indicated that p53 codon 72 Pro homozygous was associated with a two-fold risk of developing KCOT (adjusted OR (95%CI) =2.17(1.23-3.84), p=0.0062). Conclusions: The C/C genotype of P53 gene codon 72 increases the risk of developing sporadic KCOT and may be a useful tool for screening and diagnostic purposes.

두경부 편평세포암에서 HMGI(Y), p53, Ki-67의 발현과 임상인자와의 상관 관계 (Correlation of Clinical Factors with HMGI(Y), p53 and Ki-67 Expression in Squamous Cell Carcinomas of the Head and Neck)

  • 노영수;박준영;박일석;임영창;문성호;김성동;황준식;김덕환
    • 대한두경부종양학회지
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    • 제18권1호
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    • pp.11-17
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    • 2002
  • Objectives: Expression of HMGI(Y), a nucleoprotein that binds to A/T rich sequences in the minor groove of the DNA helix, is observed in neoplastically transformed cells but not in normal cells. We have analyzed HMGI(Y), p53 expression and Ki-67 labelling index in squamous cell carcinomas of the head and neck, and evaluated its clinicopathologic significance. Materials and Methods: 40 cases of squamous cell carcinoma of the head and neck were entered on the study of immunohistochemical stains for HMGI(Y), p53 and Ki-67. We analyzed the relationship between HMGI(Y), p53, Ki-67 expression and age, sex, primary tumor site, stage, survival rate, recurrence. Results: HMGI(Y) expression evidenced by immunohistochemical staining was observed in 35 of 40 (87.5%) squamous cell carcinoma of the head and neck. But no significant correlation was observed between HMGI(Y) expression and other clinical factors such as primary site, tumor stage, differenciation, cervical lymph node, metastasis, recurrence and immunohistochemical status of p53. The Ki-67 labelling index was significantly correlated with recurrence and HMGI(Y) expression (p<0.05). Conclusion: This results suggest the Ki-67 is a good prognostic factor and the HMGI(Y) expression plays some roles in carcinogenesis and cellular proliferation of squamous cell carcinoma of the head and neck. HMGI(Y) gene can be used as a cancer marker, the correlation between the gene expression and the prognosis of the cancer patient should be proved in the future studies.

ALK 유전자 다형성과 뇌출혈과의 상관성 연구 (Association between polymorphism of ALK receptor tyrosine kinase(ALK) gene and risk of intracerebral hemorrhage)

  • 김수강
    • 사물인터넷융복합논문지
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    • 제4권2호
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    • pp.21-28
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    • 2018
  • 본 연구에서는 ALK receptor tyrosine kinase (ALK) 유전자의 단일염기다형성이 뇌출혈의 발병에 관여하는 지를 연구하였다. 156명의 뇌출혈 환자와 425명의 정상인를 모집하였으며 네 개의 단일염기다형성에 대하여 상관성을 살펴보았다. 통계분석에서는 SNPstats, SPSS22.0, Haploview 프로그램을 활용하였다. Odd ratio, 95% 신뢰구간에서는 genotype 모델 및 allele 모델에서 계산하였다. 통계분석결과, rs1881421, rs1881420, rs3795850, rs2246745 의 단일염기다형성이 뇌출혈과 관련하여 유의성을 보였다. (rs1881421, OR=2.02, 95% CI=1.54-2.64, p<0.001; rs1881420, OR=0.53, 95% CI=1.16-2.01, p=0.003; rs3795850, OR=1.54, 95% CI=1.17-2.02, p=0.002; rs2246745, OR=1.95, 95% CI=1.46-2.60, p<0.001 in each allele analysis). CC, GT, and GC haplotypes 빈도 역시 유의성을 보였다. 네 개의 단일염기다형성의 minor allele 가 뇌출혈의 발병을 증가시키는데 기여하였다. 이러한 연구 결과는 ALK 유전자가 뇌출혈의 위험성과 관련 있음을 시사한다.

UBE2Q1 in a Human Breast Carcinoma Cell Line: Overexpression and Interaction with p53

  • Shafiee, Sayed Mohammad;Rasti, Mozhgan;Seghatoleslam, Atefeh;Azimi, Tayebeh;Owji, Ali Akbar
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권9호
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    • pp.3723-3727
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    • 2015
  • The p53 tumor suppressor protein is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a substrate for the ubiquitin-proteasome system, however, the ubiquitin-conjugating enzymes (E2s) involved in p53 ubiquitination have not been well studied. UBE2Q1 is a novel E2 ubiquitin conjugating enzyme gene. Here, we investigated the effect of UBE2Q1 overexpression on the level of p53 in the MDA-MB-468 breast cancer cell line as well as the interaction between UBE2Q1 and p53. By using a lipofection method, the p53 mutated breast cancer cell line, MDA-MB-468, was transfected with the vector pCMV6-AN-GFP, containing UBE2Q1 ORF. Western blot analysis was employed to verify the overexpression of UBE2Q1 in MDA-MB-468 cells and to evaluate the expression level of p53 before and after cell transfection. Immunoprecipitation and GST pull-down protocols were used to investigate the binding of UBE2Q1 to p53. We established MDA-MB-468 cells that transiently expressed a GFP fusion proteins containing UBE2Q1 (GFP-UBE2Q1). Western blot analysis revealed that levels of p53 were markedly lower in UBE2Q1 transfected MDA-MB-468 cells as compared with control MDA-MB-468 cells. Both in vivo and in vitro data showed that UBE2Q1 co-precipitated with p53 protein. Our data for the first time showed that overexpression of UBE2Q1can lead to the repression of p53 in MDA-MB-468 cells. This repression of p53 may be due to its UBE2Q1 mediated ubiquitination and subsequent proteasome degradation, a process that may involve direct interaction of UBE2Q1with p53.

Conditional Replication of a Recombinant Adenovirus Studied Using Neomycin as a Selective Marker

  • Xue, Feng;Qi, Yi-Peng;Joshua, Mallam Nock;Lan, Ping;Dong, Chang-Yuan
    • BMB Reports
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    • 제36권3호
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    • pp.275-281
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    • 2003
  • An E1B-defective adenovirus, named r2/Ad carrying the neo expression cassette, was constructed by homologous recombination. The construction, selection (using neomycin as a selective marker), and propagation of the recombinant virus was performed in human embryonic kidney 293 cells (HEK 293). An in vitro study demonstrated that this recombinant virus has the ability to replicate in and lyse some p53-deficient human tumor cells such as human glioma tumor cells (U251) and human bladder cells (EJ), but not in some cells with functional p53, such as human adenocarcinoma cells (A549) and human fibroblast cells (MRC-5). Also, based on the cytopathic effect (CPE), it was demonstrated, under identical conditions, that the U251 cells were more sensitive to r2/Ad replication than the EJ cells. In this paper, we report that r2/Ad could be very useful in studying the in vitro selective replication of E1B-defective adenovirus and has great potential in cancer gene therapy.