DNA hypomethylation and imbalanced expression of DNA methyltransferases (DNMT1, 3A, and 3B) in human uterine leiomyoma.
OBJECTIVE
Despite the high prevalence of uterine leiomyoma in women, little is known about the pathophysiology of this tumor. This study intends to define the epigenetic modulation of this tumor.


METHODS
Twenty-three pairs of leiomyomas and their adjacent myometria were collected. Status of DNA global methylation was determined by using DNA methyl acceptance assay and immunohistochemistry staining with 5-methylcytidine antibody. MRNA level of DNA methyltransferases (DNMT1, 3A, and 3B) was assessed by quantitative real time PCR.


RESULTS
DNA global hypomethylation was detected in the leiomyoma tissues as compared with the adjacent myometria. DNMT1 expression was increased in 47.5% and was equal in 47.5% in leiomyomas compared to the adjacent myometria. On the other hand, over 74% of cases showed decreased expression of DNMT3A and 3B in leiomyomas compared to the adjacent myometria.


CONCLUSIONS
Global hypomethylation and imbalanced expression of DNMTs in uterine leiomyoma suggested a potential mechanism of epigenetic modulation in the development of this tumor.
Li
Shuanfang
S
Department of Pharmacology, Tulane/Xavier Universities, 1430 Tulane Ave, New Orleans, LA 70112-2699, USA. li2@niehs.nih.gov
Chiang
Tung-chin
TC
Richard-Davis
Gloria
G
Barrett
J Carl
JC
Mclachlan
John A
JA
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000235:genetics*; 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