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2016 Fiscal Year Final Research Report

TET family proteins and 5-hydroxymethylcytosine in gastrointestinal carcinoma.

Research Project

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Project/Area Number 26461953
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionKumamoto University

Principal Investigator

MIYANARI Nobutomo  熊本大学, 医学部附属病院, 非常勤診療医師 (90336230)

Research Collaborator MURATA Asuka  熊本大学, 医学部附属病院, 非常勤診療医師 (10625768)
Project Period (FY) 2014-04-01 – 2017-03-31
KeywordsDNA脱メチル化機構 / 5-hmC発現低下 / TET酵素減少 / LINE-1メチル化レベル
Outline of Final Research Achievements

The Ten-eleven translocation (TET) enzymes (TET1, TET2, and TET3) are implicated in DNA demethylation, through dioxygenase activity that converts 5′-cytosine methylation (5-methylcytosine [5-mC]) to 5-hydroxymethylcytosine (5-hmC). We evaluated functions of 5-hmC and TET expression in esophageal squamous cell carcinoma (ESCC). 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, TET2 reduction and subsequent 5-hmC loss might affect ESCC development and progression.

Free Research Field

エピジェネティクス、消化器癌

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Published: 2018-03-22  

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