Prognostic Significance of Human Pituitary Tumor-Transforming Gene Immunohistochemical Expression in Differentiated Thyroid Cancer

Sáez, Carmen; Martínez-Brocca, María Asunción; Castilla, Carolina; Soto, Alfonso; Navarro, Elena; Tortolero, Marı́a; Pintor‐Toro, José Antonio; Japón, Miguel Á.

doi:10.1210/jc.2005-2532

Cited by 41 publications

(40 citation statements)

References 28 publications

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“…PTTG and PBF downregulate NIS expression and iodide uptake in vitro We and others have previously demonstrated that thyroid cancers show increased expression of PTTG Boelaert et al, 2003a;Saez et al, 2006), and we recently reported that PBF is also overexpressed in differentiated thyroid tumours compared with normal tissue . In addition, two reports have indicated that PTTG represses NIS and that PTTG protein expression is negatively correlated with radioiodine uptake in thyroid tumours (Saez et al, 2006).…”

Section: Nis Expression Is Reduced In Thyroid Cancermentioning

confidence: 69%

“…In addition, two reports have indicated that PTTG represses NIS and that PTTG protein expression is negatively correlated with radioiodine uptake in thyroid tumours (Saez et al, 2006). We therefore investigated whether PTTG and PBF can repress NIS expression and iodide uptake in primary thyroid cells in vitro.…”

Section: Nis Expression Is Reduced In Thyroid Cancermentioning

confidence: 95%

“…One previous study in rat thyroid FRTL-5 cells implicated the pituitary tumor transforming gene (PTTG) in the downregulation of the NIS . More recently, an association between PTTG overexpression and decreased radioiodine uptake during follow-up has been reported (Saez et al, 2006). PTTG stimulates expression of basic fibroblast growth factor (FGF-2) (Zhang et al, 1999b;Ishikawa et al, 2001) and vascular endothelial growth factor (VEGF) (McCabe et al, 2002), and has been implicated in the pathogenesis of numerous neoplastic conditions (see McCabe, 2001;Yu and Melmed, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Given that PTTG and PBF are upregulated in thyroid cancer (Boelaert et al, 2003a;Stratford et al, 2005;Saez et al, 2006) and stimulate FGF-2 expression (Zhang et al, 1999b), which has been shown to repress iodide uptake (Cocks et al, 2003), and that PTTG is associated with reduced iodide uptake in vivo (Saez et al, 2006), we assessed whether PTTG and PBF might have a direct role in the repression of NIS expression and function previously reported in thyroid tumours. Our results show that PTTG and PBF inhibit NIS messenger RNA (mRNA) expression and iodide uptake in vitro.…”

Section: Introductionmentioning

confidence: 99%

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PTTG and PBF repress the human sodium iodide symporter

et al. 2007

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The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most thyroid tumours exhibit reduced iodide uptake, although the mechanisms accounting for this remain poorly understood. Pituitary tumour transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We now show that PTTG and its binding factor PBF repress expression of sodium iodide symporter (NIS) messenger RNA (mRNA), and inhibit iodide uptake. This process is mediated at least in part through fibroblast growth factor-2. In detailed studies of the NIS promoter in rat FRTL-5 cells, PTTG and PBF demonstrated specific inhibition of promoter activity via the human upstream enhancer element (hNUE). Within this B1 kb element, a complex PAX8-upstream stimulating factor 1 (USF1) response element proved critical both to basal promoter activity and to PTTG and PBF repression of NIS. In particular, repression by PTTG was contingent upon the USF1, but not the PAX8, site. Finally, in human primary thyroid cells, PTTG and PBF similarly repressed the NIS promoter via hNUE. Taken together, our data suggest that the reported overexpression of PTTG and PBF in differentiated thyroid cancer has profound implications for activity of the NIS gene, and hence significantly impacts upon the efficacy of radioiodine treatment.

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Section: Nis Expression Is Reduced In Thyroid Cancermentioning

confidence: 69%

Section: Nis Expression Is Reduced In Thyroid Cancermentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PTTG and PBF repress the human sodium iodide symporter

et al. 2007

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“…PTTG overexpression was found to decrease iodide uptake in both rat thyroid FRTL-5 cells and human primary thyroid cells, and NIS expression was reduced in the human thyrocytes ). More recently, high PTTG expression has significantly been associated in vivo with decreased radioiodine uptake during patient follow-up (Saez et al 2006). The initial observation that PTTG may be involved in the regulation of iodide uptake led us to investigate the possibility of a similar role for PBF.…”

Section: Pbf and Iodide Uptakementioning

confidence: 99%

Expression and function of the novel proto-oncogene PBF in thyroid cancer: a new target for augmenting radioiodine uptake

Franklyn¹,

McCabe²

2011

Journal of Endocrinology

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Pituitary tumor-transforming gene (PTTG)-binding factor (PBF; PTTG1IP) was initially identified through its interaction with the human securin, PTTG. Like PTTG, PBF is upregulated in multiple endocrine tumours including thyroid cancer. PBF is believed to induce the translocation of PTTG into the cell nucleus where it can drive tumourigenesis via a number of different mechanisms. However, an independent transforming ability has been demonstrated both in vitro and in vivo, suggesting that PBF is itself a proto-oncogene. Studied in only a limited number of publications to date, PBF is emerging as a protein with a growing repertoire of roles. Recent data suggest that PBF possesses a complex multifunctionality in an increasing number of tumour settings. For example, PBF is upregulated by oestrogen and mediates oestrogen-stimulated cell invasion in breast cancer cells. In addition to a possible role in the induction of thyroid tumourigenesis, PBF overexpression in thyroid cancers inhibits iodide uptake. PBF has been shown to repress sodium iodide symporter (NIS) activity by transcriptional regulation of NIS expression through the human NIS upstream enhancer and further inhibits iodide uptake via a post-translational mechanism of NIS governing subcellular localisation. This review discusses the current data describing PBF expression and function in thyroid cancer and highlights PBF as a novel target for improving radioiodine uptake and thus prognosis in thyroid cancer.

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Inhibition of pituitary tumor‐transforming gene‐1 in thyroid cancer cells by drugs that decrease specificity proteins

Chintharlapalli

Papineni

Lee

et al. 2011

Molecular Carcinogenesis

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Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) and the corresponding 2-trifluoromethyl analog (CF3DODA-Me) are derived synthetically from the triterpenoid glycyrrhetinic acid, a major component of licorice. CDODA-Me and CF3DODA-Me inhibited growth of highly invasive ARO, DRO, K-18 and HTh-74 thyroid cancer cells and this was due, in part, to decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 that are overexpressed in these cells. CDODA-Me and CF3DODA-Me also decreased expression of Sp-dependent genes, such as survivin and vascular endothelial growth factor, and induced apoptosis. In addition, pituitary tumor-transforming gene-1 (PTTG-1) protein and mRNA levels were also decreased in thyroid cancer cells treated with CDODA-Me or CF3DODA-Me and this was accompanied by decreased expression of PTTG-1-dependent c-Myc and fibroblast growth factor 2 genes. RNA interference studies against Sp1, Sp3 and Sp4 proteins showed that in thyroid cancer cells, PTTG-1 was an Sp-dependent gene. This study demonstrates for the first time that drugs, such as CDODA-Me and CF3DODA-Me, that decrease Sp protein expression also downregulate PTTG-1 in thyroid cancer cells and therefore have potential for clinical treatment of thyroid cancer and other endocrine neoplasias where PTTG-1 is a major pro-oncogenic factor.

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Prognostic Significance of Human Pituitary Tumor-Transforming Gene Immunohistochemical Expression in Differentiated Thyroid Cancer

Abstract: Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.

Cited by 41 publications

References 28 publications

PTTG and PBF repress the human sodium iodide symporter

PTTG and PBF repress the human sodium iodide symporter

Expression and function of the novel proto-oncogene PBF in thyroid cancer: a new target for augmenting radioiodine uptake

Inhibition of pituitary tumor‐transforming gene‐1 in thyroid cancer cells by drugs that decrease specificity proteins

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