Transcriptional regulation of CacyBP/SIP gene and the influence of increased CacyBP/SIP level on gene expression pattern in colorectal cancer HCT116 cells.

The CacyBP/SIP protein is expressed at a particularly high level in brain, spleen, and various tumors. In this work, we have studied transcriptional regulation of the CacyBP/SIP gene and the influence of increased CacyBP/SIP level on gene expression in colorectal cancer HCT116 cells. We have shown that E2F1, EGR1, and CREB transcription factors bind to the CacyBP/SIP gene promoter and stimulate transcription of CacyBP/SIP gene. The role of CREB was further confirmed by the observation that forskolin, a strong activator of CREB phosphorylation/activity, increased CacyBP/SIP gene promoter activity. Moreover, we have shown that CREB dominant negative mutants, CREB133 and KCREB, inhibits CacyBP/SIP promoter activity. To check the biological significance of increased CacyBP/SIP expression/level we have applied RNA microarray analysis and have found that upregulation of CacyBP/SIP entails changes in mRNA level of many genes involved, among others, in immune processes.