Analysis of the HIV-EP2 gene abnormality in human breast cancer

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The HIV-EP2 gene is located on 6q23-q24, the region frequently deleted in breast cancer, and belongs to a family of genes that encodes large zinc finger containing transcription factor proteins. Although this gene has been implicated in the regulation of immune responses, inflammation, and cellular proliferation, its functions are largely unknown. In the present study, we investigated HIVE.PZ gene abnormalities in microdissected breast cancer tissue. For real-time PCR quantitational analysis of paired normal and tumor tissues, mRNA levels were reduced by up to 25 times. The overall median expression level in breast cancer (33 cases) was significantly lower than that in normal breast tissue (normalized median value of 4.49 versus 17.68 ; p<0.0001). However, its down-regulation was not correlated with the LOR of 6q, 16q, 17p, or 18q. Full-length 5'-RACE (rapid amplification of cDNA ends) analysis identified multiple exons in the 5'-untranslated regions (5'-UTR) with multiple transcriptional start sites, four of which were located in a large CpG island. No tissue-specific or cancer-specific usage patterns for the transcription start sites were identified by multiplex RT-PCR analysis of the 5'-UTR exons. Only faint methylation was detected in their 5' region of the island in lymphocytes, normal breast and breast cancer tissue, indicating physiological, aging and no tumor-specific methylation. Mutation screening detected only germline polymorphisms and not somatic mutation. Thus, down-regulation of the HIVEP2 genes frequently occurs and may be one of the critical genetic events responsible for breast cancer. However, its transcription may be regulated by complex mechanisms involving interactions with other factors and/or by other genetic/epigenetic mechanisms.