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

Humboldt-Universität zu Berlin, Berlín, Berlin, Germany
Oncogene (Impact Factor: 8.46). 01/2005; 23(57):9295-302. DOI: 10.1038/sj.onc.1208131
Source: PubMed


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.

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Available from: André Rosenthal, Aug 29, 2014
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    • "In accordance, a number of the breast-specific methylated transcription factors identified in this work were previously linked to breast differentiation and carcinogenesis. Thus, loss of ALX4 caused defective mouse mammary epithelial morphogenesis and ALX4 expression was reduced in breast cancers [22], GATA5 was associated with hPR-B expression in mammary cells and might contribute to breast cancer risk [23], MGMT methylation differed between DCIS and invasive breast cancers [24], SOX10 expression was linked to differentiation and transformation of myoepithelial/basal breast cells [25], ST18 is a tumor suppressor that was hypermethylated and silenced in breast cancers [26] and TP73 down-regulation led to epithelial to mesenchymal transition and marked proliferation and migration of mammary epithelial cells [27]. Of special interest, for TRIM29 it was previously reported that it could either function as a tumor suppressor in luminal ER positive breast cells [12] or as an oncogene in pancreatic, lung and various other cancers [8], [16] [7]. "
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    • "Staining intensity and pattern were scored by three independent observers blinded to the patient diagnosis (Figure 3). ST18 was found to be expressed mostly within the nucleus as previously reported (Jandrig et al., 2004), reflecting its function as a transcription factor (Yang et al., 2008). ST18 was found to be strongly overexpressed in the non-lesional epidermis of PV patients as compared with controls (P-value ¼ 0.00026). "
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    • "This is not novel since insulin expression was previously observed in brain, thymus, liver and bone marrow [21]. ST18 mRNA proved one of the most beta cell-selective transcripts but was also qPCR-detected in brain, and was previously observed in the human breast ductal cells [22]. These low expression-signals could reflect illegitimate (ectopic) expression of cell type-selective genes [23]. "
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