ST18 is a breast cancer tumor suppressor gene at human chromosome 8q11.2

Abstract

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-X 5 -Cys-X 12 -His-X 4 -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.

A Critical Role for the Neural Zinc Factor ST18 in Pancreatic β-Cell Apoptosis

“…ST18 was reported to be down-regulated in breast cancer cell lines and in a majority of breast tumors (5). Also, ectopic ST18 expression in the breast cancer cell line MCF-7 blunted colony formation in soft agar and tumor formation in a xenograft mouse model (5).…”

“…Very little is known about the regulation of ST18 expression, its biological role or its transcriptional targets. Loss of ST18 expression was reported in breast tumors and various breast cancer cell lines (5). Also, ectopic expression of ST18 reduced the tumorigenicity of MCF-7 cells (5), thereby suggesting a role for ST18 in tumor suppression.…”

A Novel 19q13 Nucleolar Zinc Finger Protein Suppresses Tumor Cell Growth through Inhibiting Ribosome Biogenesis and Inducing Apoptosis but Is Frequently Silenced in Multiple Carcinomas

“…Several ZFPs including ZAC, ST18, and ZNF382, had been reported as tumor suppressors and frequently inactivated by CpG methylation in human cancers (3)(4)(5). It is well known that the aberrant inactivation of negative mediators of cell proliferation, such as tumor suppressor genes (TSG), through promoter methylation, is frequently involved in multiple tumorigenesis (9).…”

“…Some ZFPs function as oncogenic proteins such as ZNF217 and ZNF639 (1,2), whereas others can act as tumor suppressors, such as ZAC, ST18, and ZNF382 (3)(4)(5). ZFPs bind to promoters with their zinc finger domains and activate or repress gene expression through their association proteins (1,6).…”

A Structural Analysis of DNA Binding by Myelin Transcription Factor 1 Double Zinc Fingers

“…NZF3 has been shown to be a breast cancer tumor suppressor gene (8) and has also been implicated in the regulation of mRNA levels of proapoptotic and proinflammatory genes in fibroblasts (9). The other paralog, MyT1L, has recently attracted substantial interest due to its ability to act in concert with two other transcription factors (Ascl1 and Brnd2) to transform mouse as well as human stem cells directly into functional neurons (10 -12).…”