Sp1 and kruppel-like factor family of transcription factors in cell growthregulation and cancer

The Sp/KLF family contains at least twenty identified members which include Sp1-4 and numerous kruppel-like factors. Members of the family bind with v arying affinities to sequences designated as 'Sp1 sites' (e.g., GC-boxes, C ACCC-boxes, and basic transcription elements). Family members have differen t transcriptional properties and can modulate each other's activity by a va riety of mechanisms. Since cells can express multiple family members, Sp/KL F factors are likely to make up a transcriptional network through which gen e expression can be fine-tuned. 'Sp1 site'-dependent transcription can be g rowth-regulated, and the activity, expression, and/or post-translational mo dification of multiple family members is altered with cell growth. Furtherm ore, Sp/KLF factors are involved in many growth-related signal transduction pathways and their overexpression can have positive or negative effects on proliferation. In addition to growth control, Sp/KLF factors have been imp licated in apoptosis and angiogenesis; thus, the family is involved in seve ral aspects of tumorigenesis. Consistent with a role in cancer, Sp/KLF fact ors interact with oncogenes and tumor suppressors, they can be oncogenic th emselves, and altered expression of family members has been detected in tum ors. Effects of changes in Sp/KLF factors are context-dependent and can app ear contradictory. Since these factors act within a network, this diversity of effects may arise from differences in the expression profile of family members in various cells. Thus, it is likely that the properties of the ove rall network of Sp/KLF factors play a determining role in regulation of cel l growth and tumor progression. J. Cell. Physiol. 188: 143-160, 2001. (C) 2 001 Wiley-Liss, Inc.