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

Jacques C, Fontaine JF, Franc B, Mirebeau-Prunier D, Triau S, Savagner F, Malthiery Y - Br. J. Cancer (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U694, Centre Hospitalier Universitaire d'Angers, Laboratoire de Biochimie et Biologie Mol├ęculaire, Angers, France. caroline.jacques@univ-angers.fr

ABSTRACT

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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Related in: MedlinePlus

(A) Differential expression of DAP3, ELK1, ESRRA and RUNX1 in tumours and normal thyroid (NT) samples. 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). We considered differential expression with two-sided Wilcoxon test (* for P<0.05; ** for P<0.005). The box-plot representation shows the median value of mRNA expression (bold line), the lower and upper limits of each box representing the first and third quartiles, respectively. Whiskers represent the limits of extreme measurements. P-values are shown in brackets. A set of 40 thyroid samples (10 FTA, 10 NT, 10 OTT and 10 PTC) was analysed by quantitative PCR (qPCR). Each expression level is normalised with respect to the normal tissue, the unit value representing isoexpression. We considered overexpression with one-sided Wilcoxon test (* for P<0.05; ** for P<0.005). (B) DAP3 mRNA expression levels in oncocytic thyroid adenomas (OTA) and oncocytic thyroid carcinomas (OTC). A set of twelve OTA and five OTC samples paired with normal tissue was analysed by qPCR (bottom plot). DAP3 expression levels in tumours are subtracted by paired normal levels. DAP3 gene expression is shown in seven OTA, eight OTC and four NT samples from the microarray data set (top plot). We considered overexpression with one-sided Wilcoxon test (* for P<0.05). The box-plot representations for microarray and qPCR results are as in A.
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fig2: (A) Differential expression of DAP3, ELK1, ESRRA and RUNX1 in tumours and normal thyroid (NT) samples. 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). We considered differential expression with two-sided Wilcoxon test (* for P<0.05; ** for P<0.005). The box-plot representation shows the median value of mRNA expression (bold line), the lower and upper limits of each box representing the first and third quartiles, respectively. Whiskers represent the limits of extreme measurements. P-values are shown in brackets. A set of 40 thyroid samples (10 FTA, 10 NT, 10 OTT and 10 PTC) was analysed by quantitative PCR (qPCR). Each expression level is normalised with respect to the normal tissue, the unit value representing isoexpression. We considered overexpression with one-sided Wilcoxon test (* for P<0.05; ** for P<0.005). (B) DAP3 mRNA expression levels in oncocytic thyroid adenomas (OTA) and oncocytic thyroid carcinomas (OTC). A set of twelve OTA and five OTC samples paired with normal tissue was analysed by qPCR (bottom plot). DAP3 expression levels in tumours are subtracted by paired normal levels. DAP3 gene expression is shown in seven OTA, eight OTC and four NT samples from the microarray data set (top plot). We considered overexpression with one-sided Wilcoxon test (* for P<0.05). The box-plot representations for microarray and qPCR results are as in A.

Mentions: A publicly available thyroid microarray data set (Giordano et al, 2006) showed overexpression of DAP3, ESRRA, ELK1 and RUNX1 genes in 15 OTT samples when compared with four NT samples (P<0.05, two-sided Wilcoxon test; Figure 2A). Death-associated protein 3 and ELK1 were also differentially expressed in 10 FTA and 51 PTC samples, and ESRRA in PTC.


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

Jacques C, Fontaine JF, Franc B, Mirebeau-Prunier D, Triau S, Savagner F, Malthiery Y - Br. J. Cancer (2009)

(A) Differential expression of DAP3, ELK1, ESRRA and RUNX1 in tumours and normal thyroid (NT) samples. 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). We considered differential expression with two-sided Wilcoxon test (* for P<0.05; ** for P<0.005). The box-plot representation shows the median value of mRNA expression (bold line), the lower and upper limits of each box representing the first and third quartiles, respectively. Whiskers represent the limits of extreme measurements. P-values are shown in brackets. A set of 40 thyroid samples (10 FTA, 10 NT, 10 OTT and 10 PTC) was analysed by quantitative PCR (qPCR). Each expression level is normalised with respect to the normal tissue, the unit value representing isoexpression. We considered overexpression with one-sided Wilcoxon test (* for P<0.05; ** for P<0.005). (B) DAP3 mRNA expression levels in oncocytic thyroid adenomas (OTA) and oncocytic thyroid carcinomas (OTC). A set of twelve OTA and five OTC samples paired with normal tissue was analysed by qPCR (bottom plot). DAP3 expression levels in tumours are subtracted by paired normal levels. DAP3 gene expression is shown in seven OTA, eight OTC and four NT samples from the microarray data set (top plot). We considered overexpression with one-sided Wilcoxon test (* for P<0.05). The box-plot representations for microarray and qPCR results are as in A.
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fig2: (A) Differential expression of DAP3, ELK1, ESRRA and RUNX1 in tumours and normal thyroid (NT) samples. 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). We considered differential expression with two-sided Wilcoxon test (* for P<0.05; ** for P<0.005). The box-plot representation shows the median value of mRNA expression (bold line), the lower and upper limits of each box representing the first and third quartiles, respectively. Whiskers represent the limits of extreme measurements. P-values are shown in brackets. A set of 40 thyroid samples (10 FTA, 10 NT, 10 OTT and 10 PTC) was analysed by quantitative PCR (qPCR). Each expression level is normalised with respect to the normal tissue, the unit value representing isoexpression. We considered overexpression with one-sided Wilcoxon test (* for P<0.05; ** for P<0.005). (B) DAP3 mRNA expression levels in oncocytic thyroid adenomas (OTA) and oncocytic thyroid carcinomas (OTC). A set of twelve OTA and five OTC samples paired with normal tissue was analysed by qPCR (bottom plot). DAP3 expression levels in tumours are subtracted by paired normal levels. DAP3 gene expression is shown in seven OTA, eight OTC and four NT samples from the microarray data set (top plot). We considered overexpression with one-sided Wilcoxon test (* for P<0.05). The box-plot representations for microarray and qPCR results are as in A.
Mentions: A publicly available thyroid microarray data set (Giordano et al, 2006) showed overexpression of DAP3, ESRRA, ELK1 and RUNX1 genes in 15 OTT samples when compared with four NT samples (P<0.05, two-sided Wilcoxon test; Figure 2A). Death-associated protein 3 and ELK1 were also differentially expressed in 10 FTA and 51 PTC samples, and ESRRA in PTC.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U694, Centre Hospitalier Universitaire d'Angers, Laboratoire de Biochimie et Biologie Mol├ęculaire, Angers, France. caroline.jacques@univ-angers.fr

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus