Reduced mRNA expression of the DNA demethylase, MBD2, in human colorectal and stomach cancers

被引:43
作者
Kanai, Y [1 ]
Ushijima, S [1 ]
Nakanishi, Y [1 ]
Hirohashi, S [1 ]
机构
[1] Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 1040045, Japan
关键词
DNA methylation; DNA demethylase; MBD2; carcinogenesis;
D O I
10.1006/bbrc.1999.1613
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A study was performed to evaluate the significance of aberrations of the newly identified DNA demethylase, MBD2, in human carcinogenesis. Levels of expression of DNA demethylase mRNA were examined by reverse transcription followed by real-time quantitative detection of the PCR products in 32 samples of colorectal cancer tissue, 24 stomach cancers, and the corresponding noncancerous mucosae. DNA demethylase mRNA levels normalized with glyceraldehyde-phosphate dehydrogenase (GAPDH) mRNA were reduced in 31 (97%) of the 32 colorectal cancers and in 22 (92%) of the 24 stomach cancers when compared with the levels in the corresponding noncancerous mucosae. The average levels of DNA demethylase mRNA expression normalized with GAPDH mRNA in each of the colorectal (0.81 +/- 0.55) and stomach (2.88 +/- 0.23) cancers were significantly lower than in the noncancerous mucosae (1.90 +/- 0.16 and 5.11 +/- 0.34, respectively, p < 0.0001). There was no significant association between the DNA demethylase mRNA level and malignant potential in both colorectal and stomach cancers. These data suggest that reduced expression of DNA demethylase may play a role at a certain step of multistage carcinogenesis. Reduction of DNA demethylase mRNA expression may be, if anything, one of the early events of carcinogenesis, but may not participate in the malignant progression of tumors. (C) 1999 Academic Press.
引用
收藏
页码:962 / 966
页数:5
相关论文
共 38 条
[21]  
Lei H, 1996, DEVELOPMENT, V122, P3195
[22]  
MAKOS M, 1993, CANCER RES, V53, P2715
[23]  
MAKOS M, 1993, CANCER RES, V53, P2719
[24]   DISTINCT HYPERMETHYLATION PATTERNS OCCUR AT ALTERED CHROMOSOME LOCI IN HUMAN LUNG AND COLON CANCER [J].
MAKOS, M ;
NELKIN, BD ;
LERMAN, MI ;
LATIF, F ;
ZBAR, B ;
BAYLIN, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (05) :1929-1933
[25]   5' CPG ISLAND METHYLATION IS ASSOCIATED WITH TRANSCRIPTIONAL SILENCING OF THE TUMOR-SUPPRESSOR P16/CDKN2/MTS1 IN HUMAN CANCERS [J].
MERLO, A ;
HERMAN, JG ;
MAO, L ;
LEE, DJ ;
GABRIELSON, E ;
BURGER, PC ;
BAYLIN, SB ;
SIDRANSKY, D .
NATURE MEDICINE, 1995, 1 (07) :686-692
[26]   Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases [J].
Okano, M ;
Xie, SP ;
Li, E .
NATURE GENETICS, 1998, 19 (03) :219-220
[27]   DNA methylation is a reversible biological signal [J].
Ramchandani, S ;
Bhattacharya, SK ;
Cervoni, N ;
Szyf, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (11) :6107-6112
[28]   REPLACEMENT OF 5-METHYLCYTOSINE BY CYTOSINE - A POSSIBLE MECHANISM FOR TRANSIENT DNA DEMETHYLATION DURING DIFFERENTIATION [J].
RAZIN, A ;
SZYF, M ;
KAFRI, T ;
ROLL, M ;
GILOH, H ;
SCARPA, S ;
CAROTTI, D ;
CANTONI, GL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (09) :2827-2831
[29]   The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors [J].
Robertson, KD ;
Uzvolgyi, E ;
Liang, GN ;
Talmadge, C ;
Sumegi, J ;
Gonzales, FA ;
Jones, PA .
NUCLEIC ACIDS RESEARCH, 1999, 27 (11) :2291-2298
[30]  
SAKAI T, 1991, AM J HUM GENET, V48, P880