Epigenetic alteration of the metallothionein 1E gene in human endometrial carcinomas.
Aberrant expression of metallothioneins (MTs) has been observed in several human tumors. In our microarray analysis, MT-1E was found to have much lower expression in endometrial cancer cells as compared with other types of cancer cells generated from the cervix, ovary or prostate. The result was confirmed by quantitative RT-PCR analysis of the MT-1E levels in individual cancer cells. Treatment of endometrial cancer cells with 5-azacytidine could reactivate MT-1E expression. We further analyzed the DNA methylation status of the promoter region of MT-1E using methylation-sensitive restriction enzymes HhaI and HpaII, followed by PCR. Promoter hypermethylation was detected in 42.4% (53/125) of the endometrial carcinoma samples, whilst none of the 38 normal tissues or hyperplasia samples were methylated. The mRNA levels of MT-1E were significantly lower in the methylation-positive than in the methylation-negative samples. Endometrial carcinoma samples with low MT-1E expression coincidently had low levels of estrogen receptor-alpha expression and vice versa. This phenomenon was not observed in the expression pattern between estrogen receptor-beta and MT-1E. There was no significant correlation between MT-1E methylation and any clinical parameters. In conclusion, a high frequency of cancer-specific hypermethylation of MT-1E was found in endometrial carcinomas. Its functional consequence in the development of endometrial cancer warrants further investigation.
Department of Obstetrics and Gynecology, University of Hong Kong, Queen Mary Hospital, Hong Kong, SAR, China.
Ka Yu
KY
Tse
Vincent Wing Sun
VW
Liu
David Wai
DW
Chan
Pui Man
PM
Chiu
Kar Fai
KF
Tam
Karen Kar Loen
KK
Chan
Xiao Yun
XY
Liao
Annie Nga Yin
AN
Cheung
Hextan Yuen Sheung
HY
Ngan
D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic
D047628:Estrogen Receptor alpha; C541541:MT1E protein, human; D008668:Metallothionein