Altered expression of the ZBRK1 gene in human breast carcinomas.

The ZBRK1 protein is a member of the KRAB-ZFP family. It functions as a transcriptional repressor by binding to its recognition sequence within target genes and producing a nucleoprotein complex containing its co-repressor BRCA1 and also probably the co-repressor KAP-1. Alterations that affect the ZBRK1 gene have not been reported in human tumours. For this reason, possible alterations in the ZBRK1 gene have been studied by analysing mRNA expression using real-time polymerase chain reaction (PCR), and gene sequence using single strand conformation polymorphism (SSCP) analysis and DNA sequencing, in 61 patients with primary breast carcinomas. BRCA1 mRNA expression and allelic loss were also studied in 25 of the same patients. ZBRK1 was underexpressed in 28 (45.9%) and overexpressed in 18 (29.5%) of the 61 cases. No significant association was observed between ZBRK1 mRNA expression and clinicopathological parameters. Loss of heterozygosity of the BRCA1 gene was found in 3 of 23 (13%) informative cases and BRCA1 mRNA expression was altered in 11 of 25 (44%) cases. No significant correlation was found between altered BRCA1 expression and the different types of ZBRK1 mRNA expression. Nine polymorphisms were found in the ZBRK1 sequence, with no significant differences between patients and control subjects. Altered ZBRK1 expression correlated significantly with two of these polymorphisms. A point mutation in one polymorphism and allelic loss in one patient were also observed, findings that indicate that these inactivation mechanisms do not frequently affect this gene. Altered expression of the ZBRK1 gene is therefore frequent in primary breast carcinoma. The functional significance of the polymorphisms in this gene is unclear. Copyright 2004 John Wiley & Sons, Ltd.