Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers

In this report, we describe the expression and function of human Sp5, a member of the Sp family of zinc finger transcription factors. Like other family members, the Sp5 protein contains a Cys2His2 zinc finger DNA binding domain at the C-terminus. Our experiments employing Ga14-Sp5 fusion proteins reveal multiple transcriptional domains, including a N-terminal activity domain, an intrinsic repressive element, and a C-terminal synergistic domain. Elevated expression of Sp5 was noted in several human tumors including hepatocellular carcinoma, gastric cancer, and colon cancer. To study the effects of the Sp5 protein on growth properties of human cancer cells and facilitate the identification of its downstream genes, we combined an inducible gene expression system with microarray analysis to screen for its transcriptional targets. Transfer of Sp5 into MCF-7 cells that expressed no detectable endogenous Sp5 protein elicited significant growth promotion activity. Several of the constitutively deregulated genes have been associated with tumorigenesis (CDC25C, CEA-CAM6, TMPRSS2, XBP1, MYBL1, ABHD2, and CXCL12) and Wnt/beta-Catenin signaling pathways (BAMBI, SIX1, IGFBP5, AES, and p21(WAF1)). This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against human cancers. (c) 2005 Elsevier Inc. All rights reserved.