ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2.
We have identified a gene, ST18 (suppression of tumorigenicity 18, breast carcinoma, zinc-finger protein), within a frequent imbalanced region of chromosome 8q11 as a breast cancer tumor suppressor gene. The ST18 gene encodes a zinc-finger DNA-binding protein with six fingers of the C2HC type (configuration Cys-X5-Cys-X12-His-X4-Cys) and an SMC domain. ST18 has the potential to act as transcriptional regulator. ST18 is expressed in a number of normal tissues including mammary epithelial cells although the level of expression is quite low. In breast cancer cell lines and the majority of primary breast tumors, ST18 mRNA is significantly downregulated. A 160 bp region within the promoter of the ST18 gene is hypermethylated in about 80% of the breast cancer samples and in the majority of breast cancer cell lines. The strong correlation between ST18 promoter hypermethylation and loss of ST18 expression in tumor cells suggests that this epigenetic mechanism is responsible for tumor-specific downregulation. We further show that ectopic ST18 expression in MCF-7 breast cancer cells strongly inhibits colony formation in soft agar and the formation of tumors in a xenograft mouse model.
Jandrig
Burkhard
B
Department of Tumor Genetics, Max-Delbrück-Centre for Molecular Medicine, 13092 Berlin, Germany. jandrig@mdc-berlin.de
Seitz
Susanne
S
Hinzmann
Bernd
B
Arnold
Wolfgang
W
Micheel
Burkhard
B
Koelble
Konrad
K
Siebert
Reiner
R
Schwartz
Arnfried
A
Ruecker
Karin
K
Schlag
Peter M
PM
Scherneck
Siegfried
S
Rosenthal
André
A
D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8; D019175:DNA Methylation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C497230:ST18 protein, human