Association between CpG island methylation of the WWOX gene and its expression in breast cancers.
OBJECTIVE
The aim of the present study was to evaluate the expression of the WWOX gene in breast carcinoma and to analyze the relationship between its expression and methylation.


METHODS
Methylation of the WWOX promoter and exon 1 as well as WWOX expression were determined by methylation-specific PCR, reverse transcription PCR and immunohistochemistry in 20 breast cancer tissue samples and corresponding nonneoplastic tissues. The expression of WWOX protein was evaluated by immunohistochemistry in 2 breast cancer cell lines.


RESULTS
WWOX mRNA expression was reduced in breast cancer tissues as compared to adjacent tissues (p < 0.001). WWOX mRNA and protein expression was significantly reduced in breast cancer tissues with methylated WWOX CpG islands when compared to tissues without methylation (p < 0.001 and p = 0.008, respectively). Immunohistochemical analysis also showed that WWOX levels were significantly decreased in tissues with WWOX methylation (p = 0.001). WWOX mRNA and protein expression was greatly reduced in MDA-MB-231 cells, partly due to the methylation of WWOX CpG islands, and recovered after hydralazine treatment.


CONCLUSIONS
Differential regulation of the WWOX gene plays an important role in the carcinogenesis of breast cancer, due partially to methylation of the WWOX DNA CpG islands.
Wang
X
X
Department of Breast Surgery, Jinan Central Hospital, Medical College, Jinan, China.
Chao
L
L
Jin
G
G
Ma
G
G
Zang
Y
Y
Sun
J
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D000074584:WW Domain-Containing Oxidoreductase
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human