Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?

Chiefari, Eusebio; Brunetti, Antonio; Arturi, Franco; Bidart, Jean Michel; Russo, Diego; Schlumberger, Martin; Filetti, Sébastiano

doi:10.1186/1471-2407-2-35

Cited by 110 publications

(86 citation statements)

References 18 publications

(21 reference statements)

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“…It is well known that Sp1 is constitutively overexpressed in a variety of human cancers. [42][43][44][45] In ovarian cancers, such overexpression may facilitate LTBP-1 expression in patients with G-A alleles, as was observed in the present immunohistochemical analyses. Tightly linked SNPs within or adjacent to Sp1 binding sites are also known in the promoters of other cancerrelated genes, such as EGFR, MMP-2, and vascular endothelial growth factor.…”

Section: Discussionsupporting

confidence: 56%

Novel Functional Single Nucleotide Polymorphisms in the Latent Transforming Growth Factor-β Binding Protein-1L Promoter

Higashi

Kyo

Inoue

et al. 2006

The Journal of Molecular Diagnostics

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Latent transforming growth factor (TGF)-␤ binding proteins (LTBPs) play important roles in the secretion and activation of TGF-␤. We previously reported that LTBP-1L is overexpressed in some patients with ovarian cancer. To clarify the molecular mechanism of LTBP-1L regulation , we analyzed DNA sequences in the promoter region of LTBP-1L and identified two novel single nucleotide polymorphisms , ؊202G/C and ؉20A/C. While the alleles with ؊202C and ؉20C were initially reported , our data demonstrated that ؊202G and ؉20A are common in both ovarian cancer patients and healthy patients in the Japanese population. Luciferase reporter assays revealed that the G-A haplotype induced transcriptional activation in a Sp1-dependent manner. Electrophoretic mobility shift assays showed that increased binding affinity of Sp1 to the promoter with ؊202G and ؉20A. Interestingly , ovarian cancer patients (n ‫؍‬ 42) with G-A/G-A homozygous genotype had increased expression of LTBP-1 and apparently poorer survival than those with other genotypes (P ‫؍‬ 0.02). These findings suggest that the single nucleotide polymorphisms ؊202G/C and ؉20A/C on the LTBP-1L promoter may affect the clinical outcome of ovarian cancer patients , probably via up-regulating protein expression. Further studies using a larger number of samples will definitively determine the correlation between LTBP-1 haplotype and clinical behavior of ovarian cancer. (J Mol

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Section: Discussionsupporting

confidence: 56%

Novel Functional Single Nucleotide Polymorphisms in the Latent Transforming Growth Factor-β Binding Protein-1L Promoter

Higashi

Kyo

Inoue

et al. 2006

The Journal of Molecular Diagnostics

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“…Firstly, Sp1 activity is increased following phosphorylation by oncogenic signalling pathways such as the RAS/RAF/MAPK and the PI3K/Akt pathways (Kivinen et al, 1999;Milanini-Mongiat et al, 2002;Pore et al, 2004). Secondly, Sp1 is overexpressed and/or hyperactivated in a number of human tumours (Lietard et al, 1997;Zannetti et al, 2000;Shi et al, 2001;Chiefari et al, 2002;Wang et al, 2003). Thirdly, Sp1 overexpression is required for the maintenance of the transformed phenotype as its downregulation in human fibrosarcoma cell lines inhibits their tumorigenicity (Lou et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, numerous studies have documented that Sp1 activity and/or Sp1 expression levels are elevated in various human cancers. Elevated levels of Sp1 protein have been observed in human primary gastric tumours, in pancreatic adenocarcinomas and in thyroid tumours but not in normal tissues (Shi et al, 2001;Chiefari et al, 2002;Wang et al, 2003). In gastric cancer, elevated Sp1 expression levels have been correlated with a poor survival (Yao et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Sp1 transcription factor induces apoptosis

et al. 2006

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Transcription factor Sp1 has recently been shown to be overexpressed in a number of human cancers and its overexpression contributes to malignant transformation. Sp1 regulates the expression of a number of genes participating in multiple aspects of tumorigenesis such as angiogenesis, cell growth and apoptosis resistance. To better understand the role of increased Sp1 levels on apoptosis regulation we have used retroviruses to overexpress this protein in haematopoietic Baf-3 cells and in 3T3 fibroblasts. We have also used inducible expression systems to control ectopic Sp1 levels in different cell types. Surprisingly, Sp1 overexpression on its own induces apoptosis in all the cellular models tested. The apoptotic pathways induced by Sp1 overexpression are cell type specific. Finally, using a truncated form of Sp1, we show that Sp1-induced apoptosis requires its DNA-binding domain. Our results highlight that Sp1 levels in untransformed cells must be tightly regulated as Sp1 overexpression leads to the induction of apoptosis. Our results also suggest that cancer cells overexpressing Sp1 can avoid Sp1-induced apoptosis.

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“…However, genes with multiple SP-1 promoter sites, such as oncogenes, are more likely to show modulated gene expression. Human pancreatic cancer cell lines and cancer tissue, 67 breast cancer cell lines and cancer tissue, 68 gastric carcinoma, 69 and thyroid carcinoma 70 have all shown overexpression or a higher binding activity of SP-1, which correlates with the upregulation of VEGF, 67 urokinase plasminogen activator and urokinase plasminogen activator receptor, 68 and epithelial growth factor receptor and epidermal growth factor receptor. 69,71 Wei et al 72 explored the use of COX-2 inhibition to reduce Sp1 DNA-binding and transcriptional activity.…”

Section: Crebmentioning

confidence: 99%

Transcription factors: their potential as targets for an individualized therapeutic approach to cancer

2008

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Pro-cancer signals are controlled by the expression and transcription of oncogenes. Transcription of DNA is dependent on the spatially and temporally coordinated interaction between transcriptional machinery (RNA polymerase II, transcription factors (TFs)) and transcriptional regulatory components (promoter elements, enhancers, silencers and locus control regions). Unique TFs have been identified in association with cancer. This review summarizes key oncogene-related TFs and organizes their pro-cancer activity according to the six hallmark functions (self sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of programmed cell death, limitless replicative potential, sustained angiogenesis and metastatic spread) proposed as constituting the infrastructure of the malignant process.

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Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation?

Cited by 110 publications

References 18 publications

Novel Functional Single Nucleotide Polymorphisms in the Latent Transforming Growth Factor-β Binding Protein-1L Promoter

Novel Functional Single Nucleotide Polymorphisms in the Latent Transforming Growth Factor-β Binding Protein-1L Promoter

Overexpression of Sp1 transcription factor induces apoptosis

Transcription factors: their potential as targets for an individualized therapeutic approach to cancer

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