Human colon cancer affects nearly 150,000 patients and results in 60,000 deaths in the United States per year. While several genes implicated in the development/progression of this disease have been identified, recent studies1 have indicated colon tumors lacking these genetic defects. Thus, other genes, presently unknown, must contribute to the development/progression of this disease. With the completion of the human genome project, we are interested in identifying novel genes involved in colon cancer development/progression. One set of genes of particular interest is the SCAN-KRAB domain-containing zinc finger proteins (SKZ) considering (a) their unknown biological functions and (b) their probable role in regulation of gene expression by virtue of their DNA-binding zinc fingers. Data mining for expression of SKZ genes (virtual Northern blotting) indicated reduced expression of a novel zinc finger gene (designated hereafter as SKZ1) in colon cancer. The cDNA corresponding to SKZ1 was cloned from a normal human colon cDNA library and its stable overexpression in HCT 116 colon cancer cells inhibited cell proliferation in monolayer. Additionally, compared with the vector controls, HCT 116 cells made to express SKZ1 showed fewer colonies (7 compared with 188) in soft-agar assays, indicative of diminished tumorigenic potential. Urokinase receptor (u-PAR) overexpression is a hallmark of colon cancer progression and HCT116-SKZ1 cells showed a 75 % reduction in u-PAR protein/mRNA levels. Transient expression of Flag-tagged SKZ1 indicated a nuclear localization of this protein as expected of a DNA-binding protein. Based on the presence of six tandem zinc fingers connected by the highly conserved TGEKPYX sequence, SKZ1 represents a member of the of the C2H2 family of DNA-binding proteins. In conclusion, our data suggest that SKZ1 is a novel tumor suppressor in colon cancer. 1G. Smith, F. A. Carey, J. Beattie, M. J. V. Wilkie, T. J. Lightfoot, J. Coxhead, R. C. Garner, R. J. C. Steele, and R. Wolf. Mutations in APC, Kirsten-ras and p53-alternative genetic pathways to colorectal cancer. Proc.Natl.Acad.Sci.USA 99:9433-9438, 2002.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]