Expression and methylation status of 14-3-3 sigma gene can characterize the different histological features of ovarian cancer.
We hypothesize that 14-3-3 sigma gene expression and its regulation by methylation can characterize histological types of primary human epithelial ovarian cancer. To test this hypothesis, ovarian cancer cell lines and 54 ovarian cancer tissue samples were analyzed for expression and methylation of 14-3-3 sigma gene using methylation specific PCR. The results of our experiments demonstrate that 14-3-3 sigma gene was methylated and inactivated in ES-2 ovarian cell line, which was derived from clear cell adenocarcinoma. Treatment of this cell line with demethylating agent 5-aza-2'-deoxycytidine restored the expression of 14-3-3 sigma gene. In human ovarian cancer tissues, the expression of 14-3-3 sigma protein was inactivated in most of the ovarian clear cell carcinoma tissues. Interestingly, 14-3-3 sigma protein expression was positive in significantly higher percentages of serous (89.5%), endometrioid (90%), and mucinous (81.8%) ovarian adenocarcinoma tissues. The ovarian clear cell carcinoma samples with inactivated 14-3-3 sigma protein were highly methylated, suggesting that inactivation of 14-3-3 sigma gene is through DNA methylation. Using direct DNA sequencing, 14-3-3 sigma gene methylation on all the 17 CpG sites was significantly higher in ovarian clear cell carcinoma as compared to other histological types of ovarian cancer (serous, endometrioid, and mucinous). This is the first report suggesting that 14-3-3 sigma gene expression and methylation status can characterize histological features of different types of ovarian cancer.
Kaneuchi
Masanori
M
Department of Urology, University of California, San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA.
Sasaki
Masahiro
M
Tanaka
Yuichiro
Y
Shiina
Hiroaki
H
Verma
Mukesh
M
Ebina
Yasuhiko
Y
Nomura
Eiji
E
Yamamoto
Ritsu
R
Sakuragi
Noriaki
N
Dahiya
Rajvir
R
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005092:Exonucleases / Q000235:genetics* / Q000378:metabolism*; D005095:Exoribonucleases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017422:Sequence Analysis, DNA; D013223:Statistics as Topic
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human