Overexpression of DNA methyltransferases 1, 3a, and 3b significantly correlates with retinoblastoma tumorigenesis.
DNA methyltransferases (DNMTs) 1, 3a, and 3b affect DNA promoter methylation; studies have suggested that they have important roles in the development of cancers. In this study, we analyzed the expression of DNMTs 1, 3a, and 3b; the MIB-1 labeling index; and their clinical significance in 6 normal retinas and 62 retinoblastomas using immunohistochemical analysis. We found that DNMT proteins were not expressed in normal retinas, whereas they were frequently expressed in retinoblastomas (DNMT1, 100%; DNMT3a, 98%; and DNMT3b, 92%). Compared with well-differentiated retinoblastomas, the expression of DNMTs 1 and 3a significantly increased in poorly differentiated retinoblastomas (P = .002 and P = .003, respectively); in addition, the frequency of their increased expression was high. DNMT1 expression was significantly higher in invasive retinoblastoma. Furthermore, the expression of DNMTs was positively correlated with the MIB-1 labeling index in retinoblastoma. Our findings suggest that the overexpression of DNMTs 1, 3a, and 3b may be related to retinoblastoma tumorigenesis and progression and may represent a novel approach for retinoblastoma therapy.
Qu
Yi
Y
Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, China.
Mu
Guoying
G
Wu
Yuwei
Y
Dai
Xin
X
Zhou
Fang
F
Xu
Xiaoyi
X
Wang
Yan
Y
Wei
Fengcai
F
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D000090205:DNA Methyltransferase 3A; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019572:Retinal Neoplasms / Q000235:genetics / Q000378:metabolism*; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D000097584:DNA Methyltransferase 3B
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human