Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours

Luciani, Paola; Buci, Lisa; Conforti, Barbara; Tonacchera, Massimo; Agretti, Patrizia; Elisei, Rossella; Vivaldi, A; Cioppi, Federica; Biliotti, G; Manca, Giuseppe; Vitti, Paolo; Serio, Mario; Peri, Alessandro

doi:10.1530/eje.0.1480579

Cited by 15 publications

(12 citation statements)

References 42 publications

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“…Surprisingly, the levels of specific CREB1 mRNA were lower in PTCs compared with normal thyroid (Supplementary Figure 3). Analogous results have been described earlier (Luciani et al, 2003). Post-translational mechanisms, therefore, account for the increased CREB1 protein levels in PTCs.…”

Section: Ccdc6 Inhibits Creb1 Activity Also In Human Ptcssupporting

confidence: 88%

CCDC6 represses CREB1 activity by recruiting histone deacetylase 1 and protein phosphatase 1

et al. 2010

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RET/papillary thyroid carcinoma 1 (PTC1) oncogene is frequently activated in human PTCs. It is characterized by the fusion of the intracellular kinase-encoding domain of RET to the first 101 amino acids of CCDC6. The aim of our work is to characterize the function of the CCDC6 protein to better understand the function of its truncation, that results in the loss of the expression of one allele, in the process of thyroid carcinogenesis. Here, we report that CCDC6 interacts with CREB1 and represses its transcriptional activity by recruiting histone deacetylase 1 and protein phosphatase 1 proteins at the CRE site of the CREB1 target genes. Finally, we show an increased CREB1 phosphorylation and activity in PTCs carrying the RET/PTC1 oncogene. Consistently, an increased expression of two known CREB1 target genes, AREG and cyclin A, was observed in this subgroup of thyroid papillary carcinomas. Therefore, the repression of CREB1 activity by CCDC6 has a critical function in the development of human thyroid papillary carcinomas carrying RET/PTC1 activation.

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Section: Ccdc6 Inhibits Creb1 Activity Also In Human Ptcssupporting

confidence: 88%

CCDC6 represses CREB1 activity by recruiting histone deacetylase 1 and protein phosphatase 1

et al. 2010

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“…By contrast, several other studies have shown either normal, or even increased levels of NIS mRNA (Arturi et al, 1998;Luciani et al, 2003;Saito et al, 1998;Tanaka et al, 2000) or protein (Dohan et al, 2001;Saito et al, 1998;Wapnir et al, 2003) expression in thyroid cancer. However, immunohistochemical analyses have detected NIS protein that was not located predominantly in the basolateral membrane, as found in normal thyroid tissue, but was principally in the cytoplasm (Castro et al, 1999b;Dohan et al, 2001;Wapnir et al, 2003).…”

Section: Discussionmentioning

confidence: 65%

A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

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et al. 2009

Journal of Cell Science

143

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Differentiated thyroid cancers and their metastases frequently exhibit reduced iodide uptake, impacting on the efficacy of radioiodine ablation therapy. PTTG binding factor (PBF) is a proto-oncogene implicated in the pathogenesis of thyroid cancer. We recently reported that PBF inhibits iodide uptake, and have now elucidated a mechanism by which PBF directly modulates sodium iodide symporter (NIS) activity in vitro. In subcellular localisation studies, PBF overexpression resulted in the redistribution of NIS from the plasma membrane into intracellular vesicles, where it colocalised with the tetraspanin CD63. Cell-surface biotinylation assays confirmed a reduction in plasma membrane NIS expression following PBF transfection compared with vector-only treatment. Coimmunoprecipitation and GST-pull-down experiments demonstrated a direct interaction between NIS and PBF, the functional consequence of which was assessed using iodide-uptake studies in rat thyroid FRTL-5 cells. PBF repressed iodide uptake, whereas three deletion mutants, which did not localise within intracellular vesicles, lost the ability to inhibit NIS activity. In summary, we present an entirely novel mechanism by which the proto-oncogene PBF binds NIS and alters its subcellular localisation, thereby regulating its ability to uptake iodide. Given that PBF is overexpressed in thyroid cancer, these findings have profound implications for thyroid cancer ablation using radioiodine.

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“…CREB has been shown to be involved in leukemogenesis (Perissi et al, 1999;Shankar and Sakamoto, 2004), human melanoma cell survival (Jean et al, 1998) and several endocrine tumors (Habener et al, 1989;Peri et al, 2002;Rosenberg et al, 2002a, b;Luciani et al, 2003). Also, inhibition of Erk1/Erk2 and CREB phosphorylation can inhibit growth and induce apoptosis in cells derived from human fibrosarcoma (Rabelo et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

IGF-II induces CREB phosphorylation and cell survival in human lung cancer cells

et al. 2005

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We have previously shown that lung tumors arising in MMTV-IGF-II transgenic mice displayed elevated levels of phosphorylated cAMP response element binding protein (CREB). To investigate the role that insulin-like growth factor II (IGF-II) and CREB play in human lung tumorigenesis, A549 and NCI-H358 cells were examined. In these cell lines, IGF-II administration enhances human tumor cell survival and CREB phosphorylation. Further, the effects of IGF-II on cell survival and CREB phosphorylation appeared to be mediated, at least in part, by activation of the Erk pathways, as inhibition of these signaling pathways reduced tumor cell survival and CREB phosphorylation. Specifically, Erk5 appeared as the predominant mediator of CREB phosporylation. To further verify the importance of CREB in human lung tumorigenesis, A549 and NCI-H358 cells were stably transfected with a vector containing a dominant negative CREB construct (KCREB). KCREB transfection significantly inhibited the soft agar growth of both human tumor cell lines. In contrast, overexpression of wild-type CREB in the normal human bronchial epithelial cell line, HBE135, enhanced soft agar growth. Therefore, our results indicate that CREB and its associated proteins play a significant role in lung adenocarcinoma and IGF-II induces CREB phosphorylation, at least in part, via the Erk5 signaling pathway.

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Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours

Cited by 15 publications

References 42 publications

CCDC6 represses CREB1 activity by recruiting histone deacetylase 1 and protein phosphatase 1

CCDC6 represses CREB1 activity by recruiting histone deacetylase 1 and protein phosphatase 1

A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

IGF-II induces CREB phosphorylation and cell survival in human lung cancer cells

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