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Protein expression, mRNA expression and gene amplification of DNA methyltransferase 1 in endometrial tumor tissues.

ABSTRACT: Inactivation of tumor suppressor genes by methylation is an important pathway in the multi-step process of carcinogenesis. This aim of this study was to investigate the expression of DNA methyltransferase 1 (DNMT1) which strongly contributes to the methylation process in endometrial normal and tumor tissues. Moreover, a correlation with the expression of hMLH1 and E-cadherin that was inactivated in a number of endometrial cancers was observed. Samples were obtained from 8 cases of normal endometrium, 10 cases of hyperplasia, 11 cases of atypical hyperplasia and 38 cases of carcinoma. DNMT1 expression was correlated with tumor progression (P=0.0023), as well as with the attenuation of hMLH1 and E-cadherin expression (P=0.031 and 0.031, respectively). No attenuation of hMLH1 and E-cadherin expression was observed in DNMT1-negative cases. Thus, the investigation of DNMT1 expression in clinical samples was shown to be useful in identifying the conditions that are related to general methylation. Overexpression of DNMT1 microRNA (mRNA) was mainly observed in carcinomas. Gene amplification occurred with tumor development. Gene amplification of DNMT1 was correlated with the expression of DNMT1 protein (P=0.041). In conclusion, overexpression of DNMT1 protein is caused by various factors, one of which is gene amplification.

SUBMITTER: Ikeda S

PROVIDER: S-EPMC3915343 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Protein expression, mRNA expression and gene amplification of DNA methyltransferase 1 in endometrial tumor tissues.

Ikeda Satoshi S Imura Jyoji J Suzuki Keiko K

Molecular and clinical oncology 20130320 3

Inactivation of tumor suppressor genes by methylation is an important pathway in the multi-step process of carcinogenesis. This aim of this study was to investigate the expression of DNA methyltransferase 1 (DNMT1) which strongly contributes to the methylation process in endometrial normal and tumor tissues. Moreover, a correlation with the expression of hMLH1 and E-cadherin that was inactivated in a number of endometrial cancers was observed. Samples were obtained from 8 cases of normal endomet ...[more]

PMID: 24649186

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Project description:BackgroundGene expression microarray technology permits the analysis of global gene expression profiles. The amount of sample needed limits the use of small excision biopsies and/or needle biopsies from human or animal tissues. Linear amplification techniques have been developed to increase the amount of sample derived cDNA. These amplified samples can be hybridised on microarrays. However, little information is available whether microarrays based on amplified and unamplified material yield comparable results. In the present study we compared microarray data obtained from amplified mRNA derived from biopsies of rat cardiac left ventricle and non-amplified mRNA derived from the same organ. Biopsies were linearly amplified to acquire enough material for a microarray experiment. Both amplified and unamplified samples were hybridized to the Rat Expression Set 230 Array of Affymetrix.ResultsAnalysis of the microarray data showed that unamplified material of two different left ventricles had 99.6% identical gene expression. Gene expression patterns of two biopsies obtained from the same parental organ were 96.3% identical. Similarly, gene expression pattern of two biopsies from dissimilar organs were 92.8% identical to each other.Twenty-one percent of reporters called present in parental left ventricular tissue disappeared after amplification in the biopsies. Those reporters were predominantly seen in the low intensity range. Sequence analysis showed that reporters that disappeared after amplification had a GC-content of 53.7+/-4.0%, while reporters called present in biopsy- and whole LV-samples had an average GC content of 47.8+/-5.5% (P <0.001). Those reporters were also predicted to form significantly more (0.76+/-0.07 versus 0.38+/-0.1) and longer (9.4+/-0.3 versus 8.4+/-0.4) hairpins as compared to representative control reporters present before and after amplification.ConclusionThis study establishes that the gene expression profile obtained after amplification of mRNA of left ventricular biopsies is representative for the whole left ventricle of the rat heart. However, specific gene transcripts present in parental tissues were undetectable in the minute left ventricular biopsies. Transcripts that were lost due to the amplification process were not randomly distributed, but had higher GC-content and hairpins in the sequence and were mainly found in the lower intensity range which includes many transcription factors from specific signalling pathways.

Dataset Information

Protein expression, mRNA expression and gene amplification of DNA methyltransferase 1 in endometrial tumor tissues.

Publications

Protein expression, mRNA expression and gene amplification of DNA methyltransferase 1 in endometrial tumor tissues.

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