RGD Reference Report - TET family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma. - Rat Genome Database

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TET family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma.

Authors: Murata, A  Baba, Y  Ishimoto, T  Miyake, K  Kosumi, K  Harada, K  Kurashige, J  Iwagami, S  Sakamoto, Y  Miyamoto, Y  Yoshida, N  Yamamoto, M  Oda, S  Watanabe, M  Nakao, M  Baba, H 
Citation: Murata A, etal., Oncotarget. 2015 Sep 15;6(27):23372-82.
RGD ID: 11528815
Pubmed: PMID:26093090   (View Abstract at PubMed)
PMCID: PMC4695124   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.4281   (Journal Full-text)

Mammalian DNA is epigenetically marked by 5'-cytosine methylation (5-methylcytosine [5-mC]). The Ten-eleven translocation (TET) enzymes (TET1, TET2, and TET3) are implicated in DNA demethylation, through dioxygenase activity that converts 5-mC to 5-hydroxymethylcytosine (5-hmC). Although decreased TET is reportedly associated with decreased 5-hmC levels in various cancers, functions of 5-hmC and TET expression in esophageal squamous cell carcinoma (ESCC) are unclear. We used ELISA and immunohistochemistry tests to analyze 5-hmC status in ESCC tissues, RT-qPCR to analyze TET family mRNA expression in normal and tumor tissues, and pyrosequencing to quantify LINE-1 (i.e., global DNA methylation) levels. ELISA and immunohistochemical testing showed 5-hmC levels were significantly lower in ESCC than in paired normal tissues (P < 0.0001). TET2 expression was significantly lower in ESCCs than paired normal tissues (P < 0.0001), and significantly associated with 5-hmC levels in ESCCs (P = 0.003, r = 0.33). 5-hmC levels were also significantly associated with LINE-1 methylation level (P = 0.0002, r = 0.39). Patients with low 5-hmC levels had shorter overall survival than those with higher levels, although not significantly so (P = 0.084). In conclusion, 5-hmC expression was decreased in ESCC tissues, and was associated with TET2 expression level. TET2 reduction and subsequent 5-hmC loss might affect ESCC development.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
esophagus squamous cell carcinoma  IEP 11528815mRNA:decreased expression:esophagus squamous epithelium (human)RGD 
esophagus squamous cell carcinoma  ISOTET2 (Homo sapiens)11528815; 11528815mRNA:decreased expression:esophagus squamous epithelium (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tet2  (tet methylcytosine dioxygenase 2)

Genes (Mus musculus)
Tet2  (tet methylcytosine dioxygenase 2)

Genes (Homo sapiens)
TET2  (tet methylcytosine dioxygenase 2)


Additional Information