• Title/Summary/Keyword: Mdm36

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STUDY ON MUTATION OF P53 AND EXPRESSION OF MDM-2 IN DMBA INDUCED CARCINOMA OF HAMSTER BUCCAL POUCH (DMBA로 유도된 햄스터 협낭암종에서 p53 유전자 변이와 mdm-2 단백의 발현에 관한 연구)

  • Park, Yong-Sun;Kim, Kyung-Wook;Lee, Jae-Hoon;Kim, Chang-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.5
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    • pp.373-384
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    • 2001
  • Cellular proliferation is an intricately regulated process mediated by the coordinated interactions of critical growth control genes. Two of these factors in mammalian cells are the p53 and mdm-2 genes. A protein product of the mem-2 oncogene has been recently shown to associate with the protein encoded by the tumor suppressor gene p53. The p53 tumor suppressor protein is stabilized in response to DNA damage and other stress signals and causes the cell to undergo growth arrest or apoptosis, thus preventing the establishment of mutations in future cellular generations. Mutation or loss of p53 is a very common event in tumor progression. It occurs in about 50% of all tumors analysed including of colon, lung, breast and liver. The cellular mdm-2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcoma and in other mammalian tumors. Proteins encoded by the mdm-2 gene are able to bind to the p53 protein and, when overexpressed, can inhibit p53's transcriptional activation function, thus mdm-2 can act as a negative regulator of p53 function. Experimental study was performed to observe the relationship between p53 gene mutation and mdm-2 protein expression and apply the results to the clinical activity. 36 golden syrian hamster each weighing $60{\sim}80g$ were used and painted with 0.5% DMBA by 3 times weekly on the right buccal cheek(experimental side) for 6, 8, 10, 12, 14 and 16 weeks. Left buccal cheek(control side) was treated with mineral oil as the same manner to the right side. The hamsters were sacrificed on the 6, 8, 10, 12, 14 & 16 weeks. Normal and tumor tissues from paraffin block were examined for histology and immunohistochemistry observation, and were completely dissected by microdissection and DNA from both tissue were isolated by proteins K/phenol/chloroform extraction. Segments of the hamster p53 exons 5, 6, 7 and 8 were amplified by PCR using the oligonucleotide primers, and then confirmational change was observed by SSCP respectively. The results were as follows : 1. Dysplasia at 6 weeks, carcinoma in situ at 8 weeks and invasive carcinoma from 10 weeks could be observed in experimental groups. 2. p53 mutations were detected in 10 of the 36(28%) and the exons 6(6 of the 10 : 60%) was the most hot spot area among the highy conserved region(exons 5, 6, 7 & 8). 3. Immunohistochemical study confirmed 22 of the 36(61%) of p53 expression involving 10 of p53 mutations. 4. mdm-2 expression of was showed in 3 of the 36(8%) involving 1 of the 22 of p53 expression and 2 of the 14 of p53 non-expression. From the above results, mutation of p53 gene or expression of p53 protein may have the influence of the DMBA induced carcinoma of hamster buccal pouch but the expression of mdm-2 protein may not have relationship with tumorigenesis.

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Meta-analysis of Associations between the MDM2-T309G Polymorphism and Prostate Cancer Risk

  • Chen, Tao;Yi, Shang-Hui;Liu, Xiao-Yu;Liu, Zhi-Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4327-4330
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    • 2012
  • The mouse double minute 2 (MDM2) gene plays a key role in the p53 pathway, and the SNP 309T/G single-nucleotide polymorphism in the promoter region of MDM2 has been shown to be associated with increased risk of cancer. However, no consistent results were found concerning the relationships between the polymorphism and prostate cancer risk. This meta-analysis, covering 4 independent case-control studies, was conducted to better understand the association between MDM2-SNP T309G and prostate cancer risk focusing on overall and subgroup aspects. The analysis revealed, no matter what kind of genetic model was used, no significant association between MDM2-SNP T309G and prostate cancer risk in overall analysis (GT/TT: OR = 0.84, 95%CI = 0.60-1.19; GG/TT: OR = 0.69, 95%CI = 0.43-1.11; dominant model: OR = 0.81, 95%CI= 0.58-1.13; recessive model: OR = 1.23, 95%CI = 0.95-1.59). In subgroup analysis, the polymorphism seemed more likely to be a protective factor in Europeans (GG/TT: OR = 0.52, 95%CI = 0.31-0.87; recessive model: OR = 0.58, 95%CI = 0.36-0.95) than in Asian populations, and a protective effect of the polymorphism was also seen in hospital-based studies in all models (GT/TT: OR = 0.74, 95%CI = 0.57-0.97; GG/TT: OR = 0.55, 95%CI = 0.38-0.79; dominant model: OR = 0.69, 95%CI = 0.54-0.89; recessive model: OR = 0.70, 95%CI = 0.51-0.97). However, more primary studies with a larger number of samples are required to confirm our findings.

The MDM2 SNP309T>G Polymorphism Increases Bladder Cancer Risk among Caucasians: a Meta-analysis

  • Wang, Huai-Gao;Wu, Qing-Yun;Zhou, Hui;Peng, Xin-Sheng;Shi, Meng-Jie;Li, Jie-Mei;Zhou, Yan-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5277-5281
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    • 2014
  • Published studies have evaluated associations between the MDM2 SNP309T>G polymorphism and bladder cancer susceptibility. However, these generated inconsistent results. The aim of the present investigation was to quantify the strength of association between MDM2 SNP309T>G polymorphism and bladder cancer risk by conducting a meta-analysis. We searched PubMed and Embase for related studies that had been published in English before April 1, 2014 and associations were assessed by summarizing the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Five case-control studies with a total of 972 cases and 1,012 controls were finally identified to be eligible for the meta-analysis. Overall, the results indicated that there was no significant association between the MDM2 SNP309T>G polymorphism and bladder cancer risk (for the allele model G vs. T: OR=1.08, 95% CI 0.85-1.36, p=0.54; for the co-dominant model GG vs. TT: OR=1.20, 95% CI 0.74-1.93, p=0.46; for the dominant model GG+GT vs. TT: OR=0.98, 95% CI 0.80-1.20, p=0.83; for the recessive model GG vs. GT+TT: OR=1.20, 95% CI 0.83-1.74, p=0.33). However, on subgroup analysis by ethnicity, significant associations were found in Caucasians in three models (for the allele model G vs. T: OR=1.41, 95% CI 1.10-1.81, p=0.006; for the co-dominant model GG vs. TT: OR=2.16, 95% CI 1.28-3.63, p=0.004; for the recessive model GG vs. GT+TT: OR=2.06, 95% CI 1.31-3.22, p=0.002). In summary, the present meta-analysis provides evidence that the genotype for the MDM2 SNP309T>G polymorphism may be associated with genetic susceptibility to bladder cancer among Caucasians.

The first UV fundamental plane and evidence of star formation in early-type galaxies

  • Jeong, Hyun-Jin;Yi, Suk-Young;Bureau, Martin;Davies, Roger L.
    • Bulletin of the Korean Space Science Society
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    • 2009.10a
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    • pp.36.2-36.2
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    • 2009
  • We present GALEX (Galaxy Evolution Explorer) far (FUV) and near (NUV) ultraviolet imaging of 34 nearby early-type galaxies from the SAURON representative sample of 48 E/S0 galaxies, all of which have ground-based optical imaging from the MDM Observatory. The surface brightness profiles of nine galaxies (~26 per cent) show regions with blue UV-optical colours suggesting recent star formation. Five of these (~15 per cent) show blue integrated UV-optical colours that set them aside in the NUV integrated colour-magnitude relation. These are objects with either exceptionally intense and localised NUV fluxes or blue UV-optical colours throughout. They also have other properties confirming they have had recent star formation, in particular Hbeta absorption higher than expected for a quiescent population and a higher CO detection rate. This suggests that residual star formation is more common in early-type galaxies than we are used to believe. NUV-blue galaxies are generally drawn from the lower stellar velocity dispersion (sigma_e <200 km/s) and thus lower dynamical mass part of the sample. We have also constructed the first UV Fundamental Planes and show that NUV blue galaxies bias the slopes and increase the scatters. If they are eliminated the fits get closer to expectations from the virial theorem. Although our analysis is based on a limited sample, it seems that a dominant fraction of the tilt and scatter of the UV Fundamental Planes is due to the presence of young stars in preferentially low-mass early-type galaxies.

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Induction of p53-Dependent G1 Cell Cycle Arrest by Rhus verniciflua. Stokes Extract in Human Breast Carcinoma MCF-7 Cells (MCF-7 인체 유방암 세포에서 옻나무 추출물이 p53-Dependent G1 Cell Cycle에 미치는 영향)

  • Hong, Sang-hoon;Han, Min-ho;Choi, Yung-hyun;Park, Sang-eun
    • The Journal of Internal Korean Medicine
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    • v.36 no.1
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    • pp.13-21
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    • 2015
  • Objectives : In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet. Methods : This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells. Results : Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE Conclusions : These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.

The internal UV-line-strength relations of early-type galaxies

  • Jeong, Hyun-Jin;Yi, Suk-Young K.;Bureau, Martin;Davies, Roger L.
    • The Bulletin of The Korean Astronomical Society
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    • v.36 no.2
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    • pp.66.2-66.2
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    • 2011
  • The unexpected rising flux of early-type galaxies at decreasing ultraviolet (UV) wavelengths is a long-standing mystery. One important observational constraint is the correlation between UV-optical colours and Mg2 line strengths found by Burstein et al. (1988). The simplest interpretation of this phenomenon is that the UV strength is related to the Mg line-strength. Under this assumption, we expect galaxies with larger Mg gradients to have larger UV colour gradients. By combining UV imaging from GALEX, optical imaging from MDM and SAURON integral-field spectroscopy, we investigate the spatially-resolved relationships between UV colours and stellar population properties of 34 early-type galaxies from the SAURON survey sample. We find that galaxies with old stellar populations show tight correlations between the FUV colours (FUV-V and FUV-NUV) and the Mg b index, $H{\beta}$ index and metallicity [Z/H]. We have also derived logarithmic internal radial colour, measured line strength and derived stellar population gradients for each galaxy and again found a strong dependence of the FUV-V and FUV-NUV colour gradients on both the Mg b line-strength and the metallicity gradients. In particular, global gradients of Mg b and [Z/H] with respect to the UV colour across galaxies are consistent with their local gradients within galaxies, suggesting that the global correlations also hold locally. From a simple model based on multi-band colour fits of UV upturn and UV-weak galaxies, we have identified a plausible range of parameters that reproduces the observed radial colour profiles. In these models, the centers of elliptical galaxies, where the UV flux is strong, are enhanced in metals by roughly 60% compared to UV-weak regions.

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