Candidate tumor suppressor gene SLC5A8 is frequently down-regulated by promoter hypermethylation in prostate tumor.
BACKGROUND
The prostate gland is the most common site of cancer and the third leading cause of cancer mortality in men. Solute carrier family 5 (iodide transporter), member 8 (SLC5A8) was proposed as a potential tumor suppressor gene which is silenced by epigenetic changes in various tumors. The aim of this study was to investigate the significance of DNA methylation in SLC5A8 expression in prostate tumors.


METHODS
DNA methylation status of the promoter region and expression of SLC5A8 were evaluated in prostate cancer cell lines, tumor and adjacent non-tumor prostate tissues from same prostate cancer patients, by using bisulphite-modified sequencing, RT-PCR and quantitative methylation-specific PCR (QMSP) analysis.


RESULTS
The reduced or lost expression of SLC5A8 was observed in 70% of the tumor tissues. The bisulphite-modified sequencing analysis on the prostate cancer cell lines which do not express SLC5A8 detected the densely methylated SLC5A8 promoter region. SLC5A8 was reactivated by treatment with DNA methyl transferase inhibitor, 5-azacytidine but not by trichostatin A (TSA). Higher methylation at the promoter region of SLC5A8 in primary prostate tumor tissues was detected as compared with those in adjacent non-tumor tissues (7/10, 70%).


CONCLUSIONS
These data suggested that DNA methylation in the SLC5A8 promoter region suppressed the expression of SLC5A8 in prostate tumor.
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. jong.park@moffitt.org
Jong Y
JY
Park
Weipeng
W
Zheng
Donghwa
D
Kim
Jin Q
JQ
Cheng
Nagi
N
Kumar
Nazeel
N
Ahmad
Julio
J
Pow-Sang
D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D027501:Monocarboxylic Acid Transporters; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D027682:Cation Transport Proteins; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C476760:SLC5A8 protein, human