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Gene Review

KLF10  -  Kruppel-like factor 10

Homo sapiens

Synonyms: EGR-alpha, EGRA, Krueppel-like factor 10, TGFB-inducible early growth response protein 1, TIEG, ...
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Disease relevance of KLF10


High impact information on KLF10

  • Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells [4].
  • In this study, we have characterized the expression and function in exocrine pancreatic epithelial cells of the TGFbeta-inducible early gene (TIEG), a Krüppel-like zinc finger transcription factor encoding gene previously isolated from mesodermally derived osteoblastic cells [4].
  • In addition, some of the changes observed in SWB77 were opposite to those seen in methionine-dependent tumors, including expression of p21, TRAIL-R2, and TIEG [5].
  • We have previously reported that the TGF-beta(1)-inducible transcription factor, TIEG1, induces apoptosis in a pancreas-derived cell line [6].
  • Both TGF-beta(1)- and TIEG1-induced cell death were accompanied by an increase in the generation of reactive oxygen species and a loss of the mitochondrial membrane potential preceding the morphological changes of apoptosis [6].

Biological context of KLF10

  • TIEG2 shares 91% homology with TIEG1 within the zinc finger region and 44% homology within the N terminus [7].
  • We and others have recently reported that the transforming growth factor (TGF)-beta-regulated gene TIEG encodes a new Sp1-like protein that inhibits cell growth in cultured cells [7].
  • Moreover, overexpression of TIEG in the TGFbeta-sensitive epithelial cell line PANC1 is sufficient to induce apoptosis [4].
  • However, transfected cells that overexpress TIEG mRNA and protein (TIEG-6 and TIEG-7) display changes that mimic those of MG-63 cells treated with TGF-beta, i.e. increased alkaline phosphatase activity, decreased levels of osteocalcin mRNA and protein, and decreased cell proliferation [1].
  • Upon differentiation of myeloid cells and subsequent up-regulation of CD11d expression, TIEG1 occupancy increases [8].

Anatomical context of KLF10

  • In addition, we show that the expression of TIEG is regulated by TGFbeta1 as an early response gene in pancreatic epithelial cell lines [4].
  • Overexpression of a nuclear protein, TIEG, mimics transforming growth factor-beta action in human osteoblast cells [1].
  • The degree of these changes correlated with the level of TIEG expressed in the cell lines [1].
  • In addition to osteoblastic cells, high levels of TIEG expression were detected in skeletal muscle tissue, while low or no detectable levels were found in brain, lung, liver or kidney [9].
  • In contrast, similar analyses of untreated human keratinocytes show a cytoplasmic localized TIEG protein that appears to be translocated to the nucleus after H2O2 treatment [2].

Associations of KLF10 with chemical compounds

  • Similar to E2, 16alpha-OHE1 stimulated the expression of an early response gene, a TGF-beta inducible early gene, designated TIEG, as early as 60 minutes after treatment, whereas treatment with 2-OHE1 displayed no effect [10].
  • Nitric oxide-mediated upregulation of the TGF-beta-inducible early response gene-1 (TIEG1) in human fibroblasts by mRNA stabilization independent of TGF-beta [11].
  • This paper describes the rapid, but transient, induction of TIEG steady-state messenger RNA (mRNA) levels by 17beta-estradiol (E2) in estrogen receptor (ER)-positive, human fetal osteoblastic (hFOB/ER) cells [12].
  • Furthermore, doxazosin resulted in a considerable elevation in Smad4 and TIEG protein expression (6 h) [13].

Physical interactions of KLF10


Regulatory relationships of KLF10


Other interactions of KLF10

  • In this report, we describe the identification of an E3 ubiquitin ligase, Seven in Absentia homologue-1 (SIAH1), as a TIEG1-interacting protein [14].
  • TIEG, in combination with Smad2, distinguished between N+ and N- primary tumors with a sensitivity and specificity of 75 and 85%, respectively [17].
  • Thus, TIEG2, together with TIEG1, defines a new subfamily of TGF-beta-inducible Sp1-like proteins involved in the regulation of cell growth [7].
  • TIEG and Smad7 mRNA levels were lower in non-invasive tumors compared to normal breast tissues [17].
  • TIEG in combination with Bard1 discriminated between N-/bad outcome from N-/good tumors with a sensitivity and specificity of 83 and 82%, respectively [17].

Analytical, diagnostic and therapeutic context of KLF10

  • A novel, TGF-beta-inducible early gene (TIEG) in normal human fetal osteoblasts (hFOB) has been identified using differential-display PCR [9].
  • Computer sequence analyses indicates that TIEG mRNA encodes for a 480 amino-acid protein [9].
  • Using TIEG specific polyclonal antibody and immunoprecipitation methods in normal human fetal osteoblast cells (hFOB cells), we have now demonstrated that TIEG encodes a 72-kDa protein whose levels are transiently increased at as early as 2 h of TGF-beta treatment [2].
  • Northern blotting analysis demonstrated that NO upregulates TIEG1 mRNA in a dose-dependent manner [11].
  • Scanning confocal microscopy (using polarized, laser-based immunofluorescence) shows that TIEG protein is localized in the nucleus of hFOB/ER cells, with the levels rapidly increasing after E2 treatment [12].


  1. Overexpression of a nuclear protein, TIEG, mimics transforming growth factor-beta action in human osteoblast cells. Hefferan, T.E., Reinholz, G.G., Rickard, D.J., Johnsen, S.A., Waters, K.M., Subramaniam, M., Spelsberg, T.C. J. Biol. Chem. (2000) [Pubmed]
  2. Tissue, cell type, and breast cancer stage-specific expression of a TGF-beta inducible early transcription factor gene. Subramaniam, M., Hefferan, T.E., Tau, K., Peus, D., Pittelkow, M., Jalal, S., Riggs, B.L., Roche, P., Spelsberg, T.C. J. Cell. Biochem. (1998) [Pubmed]
  3. Absence of mutations in the transforming growth factor-beta inducible early gene 1, TIEG1, in pancreatic cancer. Antonello, D., Moore, P.S., Zamboni, G., Falconi, M., Scarpa, A. Cancer Lett. (2002) [Pubmed]
  4. Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces apoptosis in pancreatic epithelial cells. Tachibana, I., Imoto, M., Adjei, P.N., Gores, G.J., Subramaniam, M., Spelsberg, T.C., Urrutia, R. J. Clin. Invest. (1997) [Pubmed]
  5. Modulation of gene expression in human central nervous system tumors under methionine deprivation-induced stress. Kokkinakis, D.M., Liu, X., Chada, S., Ahmed, M.M., Shareef, M.M., Singha, U.K., Yang, S., Luo, J. Cancer Res. (2004) [Pubmed]
  6. The transforming growth factor beta(1)-inducible transcription factor TIEG1, mediates apoptosis through oxidative stress. Ribeiro, A., Bronk, S.F., Roberts, P.J., Urrutia, R., Gores, G.J. Hepatology (1999) [Pubmed]
  7. Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth. Cook, T., Gebelein, B., Mesa, K., Mladek, A., Urrutia, R. J. Biol. Chem. (1998) [Pubmed]
  8. The zinc finger transcription factor transforming growth factor beta-inducible early gene-1 confers myeloid-specific activation of the leukocyte integrin CD11d promoter. Noti, J.D., Johnson, A.K., Dillon, J.D. J. Biol. Chem. (2004) [Pubmed]
  9. Identification of a novel TGF-beta-regulated gene encoding a putative zinc finger protein in human osteoblasts. Subramaniam, M., Harris, S.A., Oursler, M.J., Rasmussen, K., Riggs, B.L., Spelsberg, T.C. Nucleic Acids Res. (1995) [Pubmed]
  10. Direct action of naturally occurring estrogen metabolites on human osteoblastic cells. Robinson, J.A., Waters, K.M., Turner, R.T., Spelsberg, T.C. J. Bone Miner. Res. (2000) [Pubmed]
  11. Nitric oxide-mediated upregulation of the TGF-beta-inducible early response gene-1 (TIEG1) in human fibroblasts by mRNA stabilization independent of TGF-beta. Mitsumoto, M., Mitsumoto, A., Demple, B. Free Radic. Biol. Med. (2003) [Pubmed]
  12. Estrogen regulation of a transforming growth factor-beta inducible early gene that inhibits deoxyribonucleic acid synthesis in human osteoblasts. Tau, K.R., Hefferan, T.E., Waters, K.M., Robinson, J.A., Subramaniam, M., Riggs, B.L., Spelsberg, T.C. Endocrinology (1998) [Pubmed]
  13. Quinazoline-based alpha 1-adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-beta signalling and I kappa B alpha induction. Partin, J.V., Anglin, I.E., Kyprianou, N. Br. J. Cancer (2003) [Pubmed]
  14. Modulation of transforming growth factor beta (TGFbeta)/Smad transcriptional responses through targeted degradation of TGFbeta-inducible early gene-1 by human seven in absentia homologue. Johnsen, S.A., Subramaniam, M., Monroe, D.G., Janknecht, R., Spelsberg, T.C. J. Biol. Chem. (2002) [Pubmed]
  15. TGFbeta inducible early gene enhances TGFbeta/Smad-dependent transcriptional responses. Johnsen, S.A., Subramaniam, M., Janknecht, R., Spelsberg, T.C. Oncogene (2002) [Pubmed]
  16. Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2. Wahab, N.A., Weston, B.S., Mason, R.M. Exp. Cell Res. (2005) [Pubmed]
  17. Differential gene expression of TGF beta inducible early gene (TIEG), Smad7, Smad2 and Bard1 in normal and malignant breast tissue. Reinholz, M.M., An, M.W., Johnsen, S.A., Subramaniam, M., Suman, V.J., Ingle, J.N., Roche, P.C., Spelsberg, T.C. Breast Cancer Res. Treat. (2004) [Pubmed]
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