Regulation of 14-3-3sigma expression in human thyroid carcinoma is epigenetically regulated by aberrant cytosine methylation.
Increased 14-3-3sigma expression has been observed by immunohistochemistry in papillary and anaplastic tumors, but not follicular thyroid cancers. 14-3-3sigma mRNA expression and methylation status was examined in tumor cell lines and primary thyroid tissues using real-time RT-PCR, bisulfite sequencing and methylation-specific PCR. Most of the 27 CpG's in the gene's CpG island were methylated in normal thyroid, TPC-1, NPA, FTC-238 and 2-7, which did not express 14-3-3sigma. In contrast, they were unmethylated in KAK-1 and anaplastic lines KAT4 and DRO-90. 14-3-3sigma expression was not increased in thyroid carcinomas, the majority of which had a methylated CpG island. In addition, 5-aza-dC treatment increased 14-3-3sigma expression in the FTC-238 and NPA cell lines, which had low baseline expression. We conclude 14-3-3sigma expression in thyroid carcinomas is regulated by CpG island hypermethylation.
Lal
Geeta
G
Department of Surgery, Division of Surgical Oncology, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 4641 JCP, Iowa city, IA 52242, USA. Geeta-lal@uiowa.edu
Padmanabha
Lakshmi
L
Provenzano
Matthew
M
Fitzgerald
Matthew
M
Weydert
Jamie
J
Domann
Frederick E
FE
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D018899:CpG Islands; D044127:Epigenesis, Genetic; D005092:Exonucleases / Q000378:metabolism*; D005095:Exoribonucleases; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics*
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human