Regulation of clusterin expression in human cancer via DNA methylation.
OBJECTIVE
Clusterin has attracted much recent attention because of its association with tumorigenesis and the progression of human carcinomas. The present study was designed to examine the role of clusterin methylation as an indicator of clusterin expression in tumor cell lines and breast tissue samples.


METHODS
For this purpose, we used methylation-sensitive restriction analysis followed by PCR.


RESULTS
None of the non-tumoral breast samples showed expression of clusterin by immunohistochemistry, and a methylated state was found in the promoter region of the gene. However, a demethylated state was found in 5 of 6 analyzed carcinoma cell lines. Four of 5 demethylated cell lines presented moderate to strong expression of clusterin, while no expression was detected in the unmethylated cell line. The inverse correlation found in most cell lines between clusterin expression and promoter methylation was also found in most human tumors analyzed (p < 0.001). Thus, a methylated state was present in 14 carcinomas, 12 of them with a null expression of clusterin, while a demethylated state was detected in 7 breast tumor samples, with 5 of them presenting strong expression.


CONCLUSIONS
We conclude that clusterin expression is under epigenetic control via methylation of its promoter.
Serrano
Alfonso
A
Department of Immunology, Hospital Clinico Universitario, Campus Universitario Teatinos, Málaga, Spain.
Redondo
Maximino
M
Tellez
Teresa
T
Castro-Vega
Isabel
I
Roldan
M Jose
MJ
Mendez
Rosa
R
Rueda
Antonio
A
Jimenez
Eugenio
E
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D051152:Clusterin / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020014:K562 Cells; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013094:Spermatozoa / Q000378:metabolism
D051152:Clusterin