• Title/Summary/Keyword: p53 변이

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Regulation of CCAAT/enhancer Binding Protein- alpha in Ultraviolet B Responses Involves the Cooperation of p53 and Glycogen Synthase Kinase-3 (자외선 B조사시 p53와 glycogen synthase kinase-3에 의한 CCAAT/enhancer binding protein alpha의 발현조절)

  • Yoon Kyung Sil
    • Environmental Analysis Health and Toxicology
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    • v.20 no.3 s.50
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    • pp.229-235
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    • 2005
  • 태양광선,특히 자외선 B에 대한 환경적 노출은 편평세포암과 기저세포암을 포함하는 흑색선종 이외의 피부암과 크게 관련된다고 알려져 있다. 염기 류신 지퍼계 전사조절인자인 CChAT/enhancer binding protein-alpha는 표피 각질형성세포에서 다량으로 발현되었고, 각질형성세포의 증식을 억제하며 피부암 발생을 억제하는 유전자로서의 역할이 암시된 바 있다. 최근 자외선 B가 각질형성세포에서 p53에 의한 CCAAT/enhanrer binding protein-alpha의 발현을 강력하게 유도한다는 것이 보고되었다. 이러한 CCAAT/enhancer binding protein-alpha 단백질 발현의 유도는 세포 성장 억제 세포고사와 함께 일어났다. 이 연구는 glycogen synthase kinase-3 길항제가 자외선 B에 의한 CCAAT/enhancer binding protein-alpha 유도를 억제하며 변이 kinase-불활성 GSK의 강제 발현은 자외선 B가 CCAAT/enhancer binding protein-alpha전사조절부위 활성의 증가를 억제한다는 것을 보여주었다. 즉 자외선 B에 의한 CCAAT/enhancer binding protein-alpha의 유도가 p53과 활성 glycogen synthase kinase-3에 의한 것이라는 것을 증명하였다.

Lung Adenocarcinoma Mutation Hotspot in Koreans: Oncogenic Mutation Potential of the TP53 P72R Single Nucleotide Polymorphism (한국인의 폐선암 돌연변이 핫스팟: TP53 P72R Single Nucleotide Polymorphism의 발암성 돌연변이 가능성)

  • Jae Ha BAEK;Kyu Bong CHO
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.2
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    • pp.93-104
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    • 2023
  • This study aimed to identify new markers that cause lung adenocarcinoma by analyzing mutation hotspots for the top five genes with high mutation frequency in lung adenocarcinoma in Koreans by next generation sequencing (NGS) analysis. The association between TP53 mutation types and patterns with smoking, a major cause of lung cancer, was examined. The clinicopathological characteristics of lung adenocarcinoma patients with TP53 P72R SNPs were analyzed. In Korean lung adenocarcinoma cases, regardless of the smoking status, the TP53 P72R SNP was the most frequently occurring mutational hotspot, in which the nucleotide base was transversed from C to G, and the amino acid was substituted from proline to arginine at codon 72 of TP53. An analysis of the clinicopathological characteristics of lung adenocarcinoma cases with TP53 P72R SNP revealed no significant correlation with the patient's age, gender, smoking status, and tumor differentiation, but a significant correlation with low stage (P-value =0.026). This study confirmed an increase in TP53 rather than EGFR, which was reported as the most frequent mutations in lung adenocarcinoma in Koreans through NGS. Among them, TP53 P72R SNP is the most frequent regardless of smoking status.

The Overview of the Importances of Tumor Suppressor p53 for Investigating Molecular Toxicological Mechanisms of Various Environmental Mutagens (다양한 환경변이원의 분자독성학적 메커니즘 연구에 있어서 항종양 인자 p53의 중요성 고찰)

  • Jung Hwa Jin;Ryu Jae-Chun;Seo Young Rok
    • Environmental Analysis Health and Toxicology
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    • v.19 no.3
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    • pp.321-326
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    • 2004
  • The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.

Genetic Alteration of Tumor Suppressor Gene and Microsatellite in Nonsmall Cell Lung Cancer (비소세포폐암에서 종양억제유전자와 극소위성 변이에 관한 연구)

  • Shin, Tae-Rim;Hong, Young-Sook;Kim, Jhin-Gook;Chang, Jung-Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.4
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    • pp.453-465
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    • 2000
  • Background : Lung carcinogenesis is a multistage process involving alterations in multiple genes and diverse pathway. Mutational activation of oncogenes and inactivation of tumor suppressor genes, and subsequent increased genetic instability are the major genetic events. The p53 gene and FHIT gene as tumor suppressor genes contribute to the pathogenesis of lung cancer, evidenced by mutation, microsatellite instability(MI) and loss of heterozygosity(LOH). Methods : We analysed genetic mutations of p53 and FHIT gene in 29 surgical specimens of nonsmall cell lung cancer using PCR-single strand conformation polymorphism, DNA sequencing and RT-PCR. MI and LOH were analyzed in loci of D3S1285, D9S171, and TP53. Results : In 2 cases, point mutation of p53 gene was observed on exon 5. MI of 3 times and LOH of 14 times were observed in at least one locus. In terms of the location of microsatellite, D3S1285 as a marker of FH1T was observed in 5 cases out of 26 specimens; D9S171 as a marker of p16 in 5 out of 17; and TP53 as a marker of p53 in 7 out of 27. In view of histologic type, squamous cell carcinoma presented higher frequency of microsatellite alteration, compared to others. Mutation of FHIT gene was observed in 11 cases and 6 cases of those were point mutation as a silent substitution on exon 8. FHIT mRNA expression exhibited deletion on exon 6 to 9 in 4 cases among 15 specimens, presenting beta-actin normally. Conclusion : Our results show comparable frequency of genetic alteration in nonsmall cell lung cancer to previous studies of Western countries. Microsatellite analysis might have a role as a tumor marker especially in squamous cell carcinoma. Understanding molecular abnormalities involved in the pathogenesis could potentially lead to prevention, earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.

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The influence of Collar design on peri-implant marginal bone tissue (Collar design이 임플랜트 주위 변연골 흡수에 미치는 영향)

  • Kim, Jee-Hwan;Jung, Moon-Kyou;Moon, Hong-Suk;Han, Dong-Hoo
    • The Journal of Korean Academy of Prosthodontics
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    • v.46 no.1
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    • pp.53-64
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    • 2008
  • Statement of problem: Peri-implant marginal bone loss is an important factor that affects the success of implants in esthetics and function. Various efforts have been made to reduce this bone loss by improving implant design and surface texture. Previous studies have shown that early marginal bone loss is affected by implant neck designs. Purpose: The purpose of this study was to examine the influence of laser microtexturing of implant collar on peri-implant marginal bone loss. Materials and methods: Radiographical marginal bone loss was examined in patients treated with implant-supported fixed partial dentures. Marginal bone level was examined with 101 implant fixtures installed in 53 patients at three periods(at the time of implantation, prosthetic treatment and 6-month after loading). Four types of implants were examined. The differences of bone loss between implants(ITI standard) with enough biologic width and implants(ITI esthetic plus, Silhouette IC, Silhouette IC Laser-$Lok^{TM}$) with insufficient biologic width have been compared. Resorption angles were examined at the time of prosthetic delivery and 6-month after loading. Results and Conclusion: Within the limitation of this study, the following results were drawn. 1. The marginal bone loss of ITI standard and Silhouette IC Laser-$Lok^{TM}$ was less than that of ITI esthetic plus and Silhouette IC(P<0.05). The marginal bone loss between ITI standard and Silhouette IC Laser-$Lok^{TM}$ had no significant statistical difference(P>0.05). There was no significant statistical difference between marginal bone loss of ITI esthetic plus and Silhouette IC(P>0.05). 2. There was no significant difference in marginal bone loss between maxilla and mandible(P>0.05). 3. There was no significant difference in resorption angle among four types of implants(P>0.05). The marginal bone of implants with supracrestal collar design of less than that of biologic width had resorbed more than those with sufficient collar length. The roughness and laser microtexturing of implant neck seem to affect these results. If an implant with collar length of biologic width, exposure of fixture is a possible complication especially in the anterior regions of dentition that demand high esthetics. Short smooth neck implant are often recommended in these areas which may lack the distance between microgap and the marginal bone level. In these cases, the preservation of marginal bone must be put into consideration. From the result of this study, it may be concluded that laser microtexturing of implant neck is helpful in the preservation of marginal bone.

Clinical Significance of p53 Gene and nm23 Gene Expression in Esophageal Cancer (식도암 조직에시 p53 및 nm23 유전자 발현의 임상적 의의)

  • Park, Kuhn;Lee, Jong-Ho;Sa, Young-Jo;Jin, Ung;Kwon, Jong-Bum;Park, Jae-Gil;Lee, Sun-He;Kwak, Moon-Sub
    • Journal of Chest Surgery
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    • v.37 no.3
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    • pp.261-266
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    • 2004
  • Although significant progress has been made in the surgical treatment of esophageal carcinoma as well as in the detection of early stage esophageal carcinoma by diagnostic techniques, the prognosis of the esophageal carcinoma patients remain poor. The p53 gene product is known to regulate cell growth and proliferation. And the nm23 gene was identified originally as an anti-metastatic influence whose expression was correlated inversely with tumor metastatic potential in murine melanoma cell lines. This experiment was intended to know the relationship among the p53 and nm23 gene expression versus clinicopahologic characteristics of the esophageal cancer. Total 40 cases were collected from patients who had undergone esophagectomy at St. Mary's Hospital, Catholic university of Korea. Immunohistochemical stain for p53 mutant-type protein and nm23 protein was graded as <10% positive tumor cells: negative; 10∼30% positive tumor cells: + ; 30∼50% positive tumor cells: ++, and >50% positive tumor cells: +++. The tumor invasion was grades as none:- ; mild:+ ; moderate:++ ; severe: +++. Overexpression of p53 protein and nm23 was not associated with the survival and cliniocopathologic characteristics of the esophageal cancer. Moreover, the combination analysis of p53 and nm23 revealed that there was no relationship between the gene expression and the clinicopatholic characteristics of the esophageal cancer.

Expression Pattern of RB and p53 Proteins and its Correlation with Prognosis in Primary Lung Cancer (원발성 폐암에서 종양억제유전자 RB와 p53 단백질 발현양상과 예후와의 상관관계)

  • 이상용;허혜경;최필조;우종수;홍숙희
    • Journal of Chest Surgery
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    • v.29 no.11
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    • pp.1223-1231
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    • 1996
  • Immunohistochemical stains for RB and p53 tumor suppressor gene products were performed on 72 cases of resected primary lung cancer tissues to study the correlation between their expressions and the histologic types, the clinical stage, and the survival rate. The results were as follows. 1. The RB protein was altered or absent in 38 cases (52.8%), and the mutant p53 protein was detected in 35 cases (48.6%). 2. The incidences of RB and p53 protein expression were significantly different among the histologic types (p<0.05) but were not correlated with the clinical stages of lung cancer (p>0.05). 3. The two year survival rate of patients with alteration of both RB and p53 genes (RB-/p53+) was 22. 4%, and that with no alteration of both genes (RB+/p53-) was 63.1%. This difference was statistically significant (p=0.01). 4. It was shown that alteration of RB protein greatly affects the prognosis of lung carcinoma by multivariate analysis of prognostic factors. The presence or absence of RB and mutant p53 protein in tumor cells is closely related to the survival of primary lung cancer patients, and it is suggested that RB gene expression is an independent prognostic factor of primary lung cancer.

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Comparative Study of p53 Mutation and Oncoprotein Expression in Gastric Adenocarcinoma (미세절편으로 얻은 위암 조직세포에서 p53 유전자의 돌연변이와 종양단백 발현에 관한 연구)

  • Kim Chul;Joo Jai Kyun;Choi Chan;Kim Young Jin
    • Journal of Gastric Cancer
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    • v.3 no.3
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    • pp.145-150
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    • 2003
  • Purpose: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. Materials and Methods: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. Results: Immunohistochemical staining revealed eight cases as negative (less than $10\%$), twelve cases as postive (more than $10\%$). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P<0.05), However, there was no significant correlation between p53 mutation observed by DNA sequencing after laser capture microdissection and expression of p53 oncoprotein. Conclusion: These result suggest that he expression of p53 oncoprotein not to be related to the mutation of p53 gene at exons 4 through 9 in gastric cancer.

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P53 Expression in Adenoid Cystic Carcinoma of the Head and Neck (두경부 영역에 발생한 선양낭포암에서의 p53 단백 발현)

  • 김광현;성명훈;장근호;조양선
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1993.05a
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    • pp.84-84
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    • 1993
  • Overexpression of the mutant p53, derived from mutation of the p53 gene which is located on the short arm of chromosome 17 and plays a role in suppression of the tumor, was reported in some human malignancy such as breast or colon carcinoma and suggested to be a prognostic factor. The authors investigated expression of p53 protein by immunohistochemical staining using anti-p53 monoclonal antibody in the paraffin embedded blocks of the 23 patients who were diagnosed at Seoul National University Hospital as adenoid cystic carcinoma of the head and neck between 1982 and 1991, and could be followed-up. 7 cases(34%) out of the 23 cases showed p53 expression, and there was no significant association between p53 positivity and local recurrence(p=0.31) or distant metastasis(p=0.16)

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