• Title/Summary/Keyword: Suppressor gene

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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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Promyelocytic Leukemia Gene Functions and Roles in Tumorigenesis

  • Imani-Saber, Zeinab;Ghafouri-Fard, Soudeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8019-8026
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    • 2014
  • The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha ($RAR{\alpha}$). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors.

Replication and encapsidation of recombinant Turnip yellow mosaic virus RNA

  • Shin, Hyun-Il;Kim, In-Cheol;Cho, Tae-Ju
    • BMB Reports
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    • v.41 no.10
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    • pp.739-744
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    • 2008
  • Turnip yellow mosaic virus (TYMV) is a positive strand RNA virus that infects mainly Cruciferae plants. In this study, the TYMV genome was modified by inserting an extra subgenomic RNA promoter and a multiple cloning site. This modified TYMV was introduced into Nicotiana benthamiana using a Agrobacterium-mediated T-DNA transfer system (agroinfiltration). When a gene encoding $\beta$-glucuronidase or green fluorescent protein was expressed using this modified TYMV as a vector, replication of the recombinant viruses, especially the virus containing $\beta$-glucuronidase gene, was severely inhibited. The suppression of replication was reduced by co-expression of viral silencing suppressor genes, such as tombusviral p19, closteroviral p21 or potyviral HC-Pro. As expected, two subgenomic RNAs were produced from the recombinant TYMV, where the larger one contained the foreign gene. An RNase protection assay revealed that the recombinant subgenomic RNA was encapsidated as efficiently as the genuine subgenomic RNA.

SAFETY EVALUATION OF ADENOVIRUS-MEDIATED P16 GENE TRANSFER BY USING MICROARRAY AND 2D/MALDI-TOF

  • Park, Misun;Hoil Kang;Jaehee Pyo;Sinae Lim;Seungwan Jee;Miok Eom;Taikyung Ryeom;Kim, Okhee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.196-196
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    • 2002
  • p16INK4a tumor suppressor gene transfer in the non-small cell lung cancer cells by transduction of recombinant adenovirus (Ad5CMV-p16) resulted in significant inhibition of cancer cell growth (Anticancer Res., 1998, 18:3257-3261). As a safety concern, we have investigated gene and protein expression after transduction of adenoviral vector (Ad5CMV-p16) in human non-small cell lung cancer (A549) cells by using microarray and 2D gel electrophoresis/ MALDI-TOF.(omitted)

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Prognostic Role of PTEN Gene Expression and Length of Survival of Breast Cancer Patients in the North East of Iran

  • Golmohammadi, Rahim;Rakhshani, Mohammad Hassan;Moslem, Ali Reza;Pejhan, Akbar
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.sup3
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    • pp.305-309
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    • 2016
  • PTEN protein is an important tumour suppressor factor detectable by immunohistochemistry. The goal of the present study was to investigate the prognostic role of PTEN gene expression focusing on length of survival in breast cancer patients. This descriptive-analytical study was conducted on 100 breast cancer cases referred to Sabzevar hospitals in the north east of Iran between 2010 and 2011, followed up to 2015. The PTEN gene expression of tumour tissue samples was determined using specific monoclonal antibodies. The data were analyzed using Chi-square test and Fisher's exact test. Patient length of survival was analyzed after 4 years of follow-up using the Cox regression model. The PTEN gene was expressed in 70 of 100 samples, while being found at a high level in all noncancerous samples. There was an inverse significant relationship between expression of PTEN and tumour stage and grade (p<0.001). In addition, expression of PTEN in invasive ductal tumours was less than in non-invasive tumours. There was also an inverse significant relationship between the likelihood of death and PTEN gene expression (p<0.01). These findings indicate that lack of PTEN gene expression can be sign for a worse prognosis and poor survival in breast cancer.

Endogenous Gene Expression of p53 and Regulatory Subunits of Cyclic AMP-dependent Protein Kinase in Ovarian Cancer Cells (난소암 세포주에서 p53과 Cyclic AMP-dependent Protein Kinase의 Regulatory Subunit 유전자들의 발현에 관한 연구)

  • Jin Seo;Park, Woonmee;Hwang, Eun-Seong;Lee, Je-Ho;Hong, Seung-Hwan
    • The Korean Journal of Zoology
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    • v.38 no.2
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    • pp.204-211
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    • 1995
  • In an effort to develop a new therapeutic strategy for human gene therapy of solid ovarian tumor, we studied the expression of the p53 tumor suppressor Sene as well as regulatory subunits of cyclic AMP (cAMP)-dependent protein kinase in human ovarian carcinoma cells. Four cell lines (2774, Caov-3, SK-OV-3 and OVCAR-3) were selected for the analyses. The p53 transcript and protein were detected only in the 2774 cell line by Northern and Western Bnalysis. In the relatively fast growing cell line, SK-OV-3, the %rope 1 a regulstorv subunit (RIA of CAMP-dependent protein kinase was the highest among the four cell lines. The expression level of $RII\beta$ protein was low in the four cell lines examined. These results maw point to a direction to select the target gene(sl to be employed for gene therapy to control the ovarian cancer.

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Phenotypic and Transcriptomic Analysis of Nicotiana benthamiana Expressing Cucumber mosaic virus 2b gene (오이모자이크바이러스 2b 유전자 발현 담배의 형태 및 전사체 분석)

  • Sohn, Seong-Han;Kim, Yoon-Hee;Ahn, Yul-Kyun;Kim, Do-Sun;Won, So-Yoon;Kim, Jung-Sun;Choi, Hong-Soo
    • Research in Plant Disease
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    • v.21 no.3
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    • pp.186-192
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    • 2015
  • Cucumber mosaic virus possesses 2b gene known as a suppressor of post-transcriptional gene silencing (PTGS). To investigate its function and effect in plant, transgenic Nicotiana benethamiana expressing 2b gene was developed and analyzed in phenotypic characteristics and differential gene expression (DEG) comparing with wild-type. Eight lines of transgenic plants ($T_0$) were obtained with difficulty and showed severe deformed phenotypes in leaves, flowers, petioles and etc. Moreover, transgenic plants were hardly able to set seeds, but small amounts of seeds were barely produced in some of transgene-hemizygous plants. DEG analysis showed that transgenic plant ectopically accumulated diverse RNA transcripts at higher levels than wild-type probably due to the disturbance in RNA metabolism, especially of RNA decay, caused by 2b-mediated inhibition of PTGS. These ectopic accumulations of RNAs disrupt protein and RNA homeostasis and then subsequently lead to abnormal phenotypes of transgenic plants.

Mutations of p53 Tumor Suppressor Gene in Human Lung Cancer Cell Lines (사람 폐암세포주에서 p53 종양억제유전자의 변이)

  • Hong, Weon-Seon;Hong, Seok-Il;Lee, Dong-Soon;Son, Young-Sook;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.6
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    • pp.653-658
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    • 1993
  • Background: Recent advancement of molecular genetics has revealed that malignant transformation of a cell may be a complex multistep process and this process is grouped, in general, into two distinct categories, activation of protooncogenes and inactivation of tumor suppressor genes. This study was focused on the mutation of p53 tumor suppressor gene, because p53 gene mutation is now generally accepted to be one of the most frequent genetic changes in a variety of human cancers. Although lung cancer is one of the common cancers in Korea, the genetic change in the carcinogenesis process is not yet known clearly. To investigate the role of p53 gene mutation in lung cancer, we examined the mutations of exon 4-8 of the p53 gene in humna lung cancer cell lines, because most of the mutations of p53 gene have been reported to develop in exon 4-8. Method: Genomic DNA was obtained by the digestion of proteinase K and the extraction by phenol-chloroform-ethanol method from two human pulmonary adenocarcinoma cell lines, PC-9 and PC-14, and one human small cell lung cancer cell line, H69. To detect the mutations of exon 4-8 of the p53 gene, polymerase chain reaction single-strand conformation polymorphism(PCR-SSCP) analysis was performed with the DNA extracted from the cells. Results: The mutation of p53 gene was present in all three cell lines tested. In PC-9, PC-14 and H69, the altered mobility was detected in exon 7, 7 and 5, respectively. Conclusion: These results suggest that p53 gene mutation plays an important role in certain steps of the carcinogenesis of human non-small cell and small cell lung cancer.

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Identification of Tumor Suppressor Genes on Chromosome 21 (제21번 염색체의 종양억제유전자 발굴)

  • Lee, Eung-Bae;Choi, Jin-Eun;Jang, Jin-Sung;Park, Jae-Yong
    • Journal of Chest Surgery
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    • v.42 no.2
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    • pp.141-147
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    • 2009
  • Background: We performed this study to identify the tumor suppressor genes located in the long arm of chromosome 21 in non-small cell lung cancer. Material and Method: The genes of USP25 in 21q11.2, NCAM2, ADAMTS1 in 21q21.2, and Claudin-8 (CLDN8), Claudin-17 (CLDN17) and TIAM1 in 21q22.1 were investigated for their gene expressions, genetic alterations and promoter methylation. Result: The expressions of CLDN8 and CLDN17 were significantly decreased in 7 (L132, H157, H358, H522, H1299, H1703 and HCC2108) of 13 cell lines, and the expression of ADAMTS1 was also significantly reduced in 6 cell lines (A549, SW900, H1299, H1373, H1703 and H1793). There were no genetic alterations by PCR-SSCP and cDNA cloning in the cell lines with a decreased gene. In the cell lines with a decreased gene expression, the mRNA expression was increased significantly with treatment of 5-Aza-CdR. Conclusion: These results suggest that the ADMTS1, CLDN8 and CLDN17 may act as tumor suppressor genes.

TET2 Promoter DNA Methylation and Expression in Childhood Acute Lymphoblastic Leukemia

  • Bahari, Gholamreza;Hashemi, Mohammad;Naderi, Majid;Taheri, Mohsen
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3959-3962
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    • 2016
  • The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our ndings indicated that promoter methylation of TET2 signi cantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was signi cantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to con rm our ndings.