Epigenetic Alteration of the Metallothionein 1E Gene in Human Endometrial Carcinomas

Tse, Ka Yu; Liu, Vincent Wing Sun; Chan, David; Chiu, Pei-Chen; Tam, Kwok-kan; Chan, Karen Kar Loen; Liao, Xiao Y; Cheung, Annie N.Y.; Ngan, Hextan Y.S.

doi:10.1159/000218032

Cited by 18 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The aberrant MT1E promoter methylation was frequently observed in PCa tissues, but almost never occurred in NPT. MT1E promoter hypermethylation was previously reported only in melanoma and endometrial cancer patients [ 20 , 21 ], but, to the best of our knowledge, has never been assessed in PCa.…”

Section: Discussionmentioning

confidence: 98%

Decreased expression of MT1E is a potential biomarker of prostate cancer progression

et al. 2017

View full text Add to dashboard Cite

Differentiation of indolent and aggressive prostate carcinoma (PCa) at the time of diagnosis is currently one of the major challenges. This study aimed at identification of prognostic biomarkers to aid in predicting biochemical recurrence (BCR) of the disease. Microarray-based gene expression profiling in tissues of 8 BCR and 8 No-BCR cases revealed expression differences of 455 genes, most of which were down-regulated in BCR cases. Eleven genes were selected for validation by real-time PCR in the first PCa cohort (N = 55), while seven of them were further validated in the second, independent, PCa cohort (N = 53). Down-regulation of MT1E (p < 0.001) and GPR52 (p = 0.002) expression and up-regulated levels of EZH2 (p = 0.025) were specific biomarkers of BCR in at least one of the two PCa cohorts, but only MT1E expression retained the independent prognostic value in a multivariate analysis (p < 0.001). DNA methylation analysis (114 PCa and 24 non-cancerous tissues) showed frequent MT1E methylation in PCa (p < 0.001) and was associated (p < 0.010) with the down-regulated expression in one PCa cohort. The results of our study suggest MT1E down-regulation as a potential feature of aggressive PCa.

show abstract

Section: Discussionmentioning

confidence: 98%

Decreased expression of MT1E is a potential biomarker of prostate cancer progression

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The related agent 5-azacytidine augmented expression of the DNA repair enzyme ERCC1 by reducing its promoter methylation, and thereby decreased tumor cell sensitivity to radiation [52]. Tumor cell expression of metallothioneins (which may be important in chemotherapy resistance [4]) was also reduced by promoter methylation and augmented by 5-azacytidine [53]. …”

Section: Discussionmentioning

confidence: 99%

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors

et al. 2014

View full text Add to dashboard Cite

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy >3 months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = −0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P <0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = −0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation.

show abstract

“…Epigenetic gene silencing through DNA methylation has been suggested to be one of the important steps during endometrial carcinogenesis [23, 24, 26–28]. Promoter hypermethylation of RASSF1A, metallothionein 1E, and related tumor-suppressor genes have been found to correlate with clinicopathological parameters in endometrial cancer [23, 26, 28]. On the other hand, hypomethylation is also found to be important in regulating the expression of the S100A4 gene in endometrial cancer [27].…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of SOX2 Promoter in Endometrial Carcinogenesis

Wong

Huo

Siu

et al. 2010

Obstetrics and Gynecology International

View full text Add to dashboard Cite

This paper aimed at investigating the expression and methylation profiles of SOX2, a gene coding for the stem cell-related transcription factor SOX2, in endometrial carcinomas. By methylation-specific polymerase chain reaction (MS-PCR), the methylation status of SOX2 promoter region in 72 endometrial carcinomas and 12 normal endometrial samples was examined. Methylated allele was found in 37.5% (27/72) of endometrial carcinomas but only in 8.3% (1/12) of normal endometrial, significantly more frequent in cancers (P = .0472). SOX2 mRNA level was significantly reduced in endometrial carcinoma compared with nonneoplastic endometrium (P = .045). A significant correlation between SOX2 mRNA expression and hypermethylation of SOX2 was found (P = .024). Hypermethylation of SOX2 tended to be more frequently found in type II serous or clear cell adenocarcinoma. SOX2 methylation was also significantly correlated with shorter survival of patients (P = .046). In conclusion, epigenetic mechanisms may play a crucial role on the transcriptional regulation of SOX2 and loss of SOX2 expression may be related to endometrial carcinogenesis.

show abstract

Epigenetic Alteration of the Metallothionein 1E Gene in Human Endometrial Carcinomas

Cited by 18 publications

References 23 publications

Decreased expression of MT1E is a potential biomarker of prostate cancer progression

Decreased expression of MT1E is a potential biomarker of prostate cancer progression

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors

Hypermethylation of SOX2 Promoter in Endometrial Carcinogenesis

Contact Info

Product

Resources

About