Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation.
We analyzed Wilms' tumor suppressor 1 (WT1) expression and its regulation by promoter methylation in a panel of normal breast epithelial samples and primary carcinomas. Contrary to previous reports, WT1 protein was strongly expressed in primary carcinomas (27 of 31 tumors) but not in normal breast epithelium (1 of 20 samples). Additionally, the WT1 promoter was methylated in 6 of 19 (32%) primary tumors, which nevertheless expressed WT1. The promoter is not methylated in normal epithelium. Thus, although tumor-specific methylation of WT1 is established in primary breast cancer at a low frequency, other transcriptional regulatory mechanisms appear to supercede its effects in these tumors. Our results demonstrate expression of WT1 in mammary neoplasia, and that WT1 may not have a tumor suppressor role in breast cancer.
Loeb
D M
DM
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Evron
E
E
Patel
C B
CB
Sharma
P M
PM
Niranjan
B
B
Buluwela
L
L
Weitzman
S A
SA
Korz
D
D
Sukumar
S
S
D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002461:Cell Line, Transformed; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D016162:Genes, Wilms Tumor / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D025721:WT1 Proteins