Two-Step Differential Expression Analysis Reveals a New Set of Genes Involved in Thyroid Oncocytic Tumors

Jacques, Caroline; Baris, Olivier; Prunier-Mirebeau, Delphine; Savagner, Frédérique; Rodien, Patrice; Rohmer, V.; Franc, Brigitte; Guyétant, Serge; Malthièry, Yves; Reynier, Pascal

doi:10.1210/jc.2004-1337

Cited by 102 publications

(75 citation statements)

References 31 publications

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“…Using a two-step differential expression analysis of six Hürthle cell FTA and their paired normal tissues, Jacques et al (2005) found 30 overexpressed sequences in the tumoral tissues. Out of these 30 sequences, 12 were mtDNA encoded (ten genes from OXPHOS, the 16S rRNA gene and one noncoding sequence from D-Loop) and 18 nuclear encoded.…”

Section: Alterations In Gene Expression In Hü Rthle Cell Tumorsmentioning

confidence: 99%

“…Hürthle cell tumors display a striking upregulation of mtDNA genes and of genes implicated in protein metabolism. The authors concluded that mitochondrial proliferation appears to be associated with intense protein turnover, suggesting that such turnover is necessary for the mitochondrial proliferation and/or that the mitochondrial saturation of the cytoplasm disturbs cell trafficking and processing of proteins (Jacques et al 2005). It would be interesting to compare these results with those obtained in non-Hürthle cell tumors to evaluate the specificity of the data.…”

Section: R136mentioning

confidence: 99%

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The biology and the genetics of Hürthle cell tumors of the thyroid

Máximo¹,

Lima²,

Prazeres³

et al. 2012

Endocrine-Related Cancer

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The biology and the genetics of Hü rthle cell tumors are reviewed starting from the characterization and differential diagnosis of the numerous benign and malignant, neoplastic and nonneoplastic lesions of the thyroid in which Hü rthle cell transformation is frequently observed. The clinicopathologic and molecular evidence obtained from the comparative study of the aforementioned conditions indicate that Hü rthle cell appearance represents a phenotype that is superimposed on the genotypic and conventional histopathologic features of the tumors. Hürthle cell tumors differ from their non-Hü rthle counterparts regarding the prevalence of large deletions of mitochondrial DNA (mtDNA), mutations of mtDNA genes coding for oxidative phosphorylation (OXPHOS) proteins (namely mutations of complex I subunit genes) and mutations of nuclear genes coding also for mitochondrial OXPHOS proteins. Such mitochondrial alterations lead to energy production defects in Hü rthle cell tumors; the increased proliferation of mitochondria may reflect a compensatory mechanism for such defects and is associated with the overexpression of factors involved in mitochondrial biogenesis. The mitochondrial abnormalities are also thought to play a major role in the predisposition for necrosis instead of apoptosis which seems to be blocked in most Hü rthle cell tumors. Finally, the results obtained in experimental models using cybrid cell lines and the data obtained from histopathologic and molecular studies of familial Hü rthle cell tumors are used, together with the aforementioned genetic and epigenetic alterations, to progress in the understanding of the mechanisms through which mitochondrial abnormalities may be involved in the different steps of thyroid carcinogenesis, from tumor initiation to metastization.

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Section: Alterations In Gene Expression In Hü Rthle Cell Tumorsmentioning

confidence: 99%

Section: R136mentioning

confidence: 99%

The biology and the genetics of Hürthle cell tumors of the thyroid

Máximo¹,

Lima²,

Prazeres³

et al. 2012

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…Among these 126 genes, the Mitochondrial Ribosomal Protein Large subunit 49 (MRPL49) and 13 genes coding for subunits of the OXPHOS complexes were represented (Baris et al, 2004). A two-step study on the basis of differential display and macroarray analysis of six oncocytic thyroid adenoma samples showed that 12 of the 30 genes upregulated at least two-fold in the tumours were mtDNA-encoded genes (Jacques et al, 2005). Similarly to the data in renal and We used a public microarray data set (Giordano et al, 2006) containing data for 10 follicular thyroid adenomas (FTA), four NT, 15 oncocytic thyroid tumours (OTT) and 51 papillary thyroid carcinomas (PTC).…”

Section: Discussionmentioning

confidence: 99%

“…Tumour samples (100) and normal conterparts (61) were used for tissue array construction, where each sample were represented by three spots (0.6 mm diameter); immunostaining was carried out using the standard avidin -biotin peroxidase technique as described earlier (Kononen et al, 1998;Jacques et al, 2005). The primary antibody was either a monoclonal anti-DAP3 (Transduction Laboratories, Lexington, UK; 1/50) or a monoclonal antibody against a mitochondrial subunit of the respiratory chain complex IV (clone 113-1, Biogenex laboratories, Inc., San Ramon, CA, USA; dilution 1/50).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours

et al. 2009

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BACKGROUND: The human death-associated protein 3 (hDAP3) is a GTP-binding constituent of the small subunit of the mitochondrial ribosome with a pro-apoptotic function. METHODS: A search through publicly available microarray data sets showed 337 genes potentially coregulated with the DAP3 gene. The promoter sequences of these 337 genes and 70 out of 85 mitochondrial ribosome genes were analysed in silico with the DAP3 gene promoter sequence. The mitochondrial role of DAP3 was also investigated in the thyroid tumours presenting various mitochondrial contents. RESULTS: The study revealed nine transcription factors presenting enriched motifs for these gene promoters, five of which are implicated in cellular growth (ELK1, ELK4, RUNX1, HOX11-CTF1, TAL1-ternary complex factor 3) and four in mitochondrial biogenesis (nuclear respiratory factor-1 (NRF-1), GABPA, PPARG-RXRA and estrogen-related receptor alpha (ESRRA)). An independent microarray data set showed the overexpression of ELK1, RUNX1 and ESRRA in the thyroid oncocytic tumours. Exploring the thyroid tumours, we found that DAP3 mRNA and protein expression is upregulated in tumours presenting a mitochondrial biogenesis compared with the normal tissue. ELK1 and ESRRA were also showed upregulated with DAP3. CONCLUSION: ELK1 and ESRRA may be considered as potential regulators of the DAP3 gene expression. DAP3 may participate in mitochondrial maintenance and play a role in the balance between mitochondrial homoeostasis and tumourigenesis.

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“…SENP1 mRNA levels are elevated in thyroid oncocytic adenocarcinoma (6) and human prostate cancer (PCa) 3 (10). In addition, using in situ hybridization, we recently found greater SENP1 mRNA levels in precancerous prostatic intraepithelial neoplasia (PIN) compared with adjacent normal prostate epithelia (10).…”

mentioning

confidence: 99%

SENP1 Induces Prostatic Intraepithelial Neoplasia through Multiple Mechanisms

Bawa-Khalfe

Cheng

Lin

et al. 2010

Journal of Biological Chemistry

101

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SUMOylation has been shown to modulate DNA replication/ repair, cell cycle progression, signal transduction, and the hypoxic response. SUMO (small ubiquitin-like modifier)-specific proteases regulate SUMOylation, but how changes in the expression of these proteases contribute to physiological and/or pathophysiological events remains undefined. Here, we show that SENP1 (sentrin/SUMO-specific protease 1) is highly expressed in human prostate cancer specimens and correlates with hypoxia-inducing factor 1␣ (HIF1␣) expression. Mechanistic studies in a mouse model indicate that androgen-driven expression of murine SENP1 leads to HIF1␣ stabilization, enhanced vascular endothelial growth factor production, and angiogenesis. Further pathological assessment of the mouse indicates that SENP1 overexpression induces transformation of the normal prostate gland and gradually facilitates the onset of high-grade prostatic intraepithelial neoplasia. Consistent with cell culture studies, SENP1 enhances prostate epithelial cell proliferation via modulating the androgen receptor and cyclin D 1 . These results demonstrate that deSUMOylation plays a critical role in prostate pathogenesis through induction of HIF1␣-dependent angiogenesis and enhanced cell proliferation.SUMO (small ubiquitin-like modifier) modification of protein substrates is a dynamic process that modulates the target protein's expression, function, and/or subcellular location (1, 2). SUMOylation is regulated by SUMO-specific activating (E1), conjugating (E2), and ligating (E3) enzymes and reversed by a family of sentrin/SUMO-specific proteases (3-5). These enzymes are critical for maintaining a balance between the level of SUMOylated and unmodified cellular substrates and hence play an important role in mediating normal cellular physiology.Several large-scale gene expression studies report changes in the levels of SUMO E1, E2, and SENP1 (sentrin/SUMO-specific protease 1) in various cancers, suggesting an imbalance in the SUMO system (6 -9). SENP1 mRNA levels are elevated in thyroid oncocytic adenocarcinoma (6) and human prostate cancer (PCa) 3 (10). In addition, using in situ hybridization, we recently found greater SENP1 mRNA levels in precancerous prostatic intraepithelial neoplasia (PIN) compared with adjacent normal prostate epithelia (10). Transformation of the normal prostate epithelia to carcinoma is preceded by the development of this well characterized PIN state (11). The presence of elevated SENP1 levels in this precursor state posed the question as to whether SENP1 induction is not associated merely with the carcinoma but instead could directly contribute to prostate carcinogenesis.Recently, we demonstrated that SENP1 enhances the stability of hypoxia-inducing factor 1␣ (HIF1␣) and, consequently, HIF1␣-mediated transcription; in the absence of SENP1, HIF1␣ is actively SUMOylated and subsequently degraded under hypoxic conditions (12). In prostate carcinogenesis, hypoxic tissue environments emerge due to rapidly proliferating cancer cells, and HIF1␣ is post...

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Two-Step Differential Expression Analysis Reveals a New Set of Genes Involved in Thyroid Oncocytic Tumors

Cited by 102 publications

References 31 publications

The biology and the genetics of Hürthle cell tumors of the thyroid

The biology and the genetics of Hürthle cell tumors of the thyroid

Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours

SENP1 Induces Prostatic Intraepithelial Neoplasia through Multiple Mechanisms

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