Sp1 and krüppel‐like factor family of transcription factors in cell growth regulation and cancer

Abstract

The Sp/KLF family contains at least twenty identi®ed members which include Sp1-4 and numerous kru È ppel-like factors. Members of the family bind with varying af®nities to sequences designated as`Sp1 sites' (e.g., GC-boxes, CACCC-boxes, and basic transcription elements). Family members have different transcriptional properties and can modulate each other's activity by a variety of mechanisms. Since cells can express multiple family members, Sp/KLF factors are likely to make up a transcriptional network through which gene expression can be ®ne-tuned. Sp1 site'-dependent transcription can be growth-regulated, and the activity, expression, and/or post-translational modi®cation of multiple family members is altered with cell growth. Furthermore, 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 implicated in apoptosis and angiogenesis; thus, the family is involved in several aspects of tumorigenesis. Consistent with a role in cancer, Sp/ KLF factors interact with oncogenes and tumor suppressors, they can be oncogenic themselves, and altered expression of family members has been detected in tumors. Effects of changes in Sp/KLF factors are context-dependent and can appear contradictory. Since these factors act within a network, this diversity of effects may arise from differences in the expression pro®le of family members in various cells. Thus, it is likely that the properties of the overall network of Sp/KLF factors play a determining role in regulation of cell growth and tumor progression.

Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide

“…Additionally, Sp1 binding sites are found in the promoters of many housekeeping genes (Black and Azizkhan-Clifford, 1999). Therefore, it has been widely accepted that Sp1 functions as a basal transcription factor and Sp1 binding sites represent constitutive promoter elements to support basal transcription in these promoters (Black et al, 2001). Recent investigations indicate that Sp1 sites are involved in growth regulation (Chen et al, 2000).…”

Overexpression of Sp1 transcription factor induces apoptosis

“…In that respect, it is interesting to note that Sp1 participates in the regulation of genes involved in all these aspects of tumorigenesis (Black et al, 2001). Moreover, numerous studies have documented that Sp1 activity and/or Sp1 expression levels are elevated in various human cancers.…”

“…The promoters of many antiapoptotic genes (bcl-2, bcl-x, survivin) as well as many proapoptotic genes (bax, trail, fas, fas-ligand, caspase-8 and caspase-3) contain Sp1-binding sites (Black et al, 2001). Although embryonic stem cells with inactivated Sp1 are viable, and grow and differentiate normally, Sp1 deficient embryos are retarded in development and die after day 10 of gestation (Marin et al, 1997).…”

Analysis of human prostate cancers and cell lines for mutations in the TP53 and KLF6 tumour suppressor genes

“…Krüppel-like factors serve as core transcription factors and participate in regulation of numerous mammalian genes (Bieker, 2001;Black et al, 2001). One of the factors, KLF6, is thought to play a role in repair of vascular injury and in tissue remodelling (Kojima et al, 2000).…”