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

Jacques, Caroline; Fontaine, Jean-Fred; Franc, Brigitte; Mirebeau‐Prunier, Delphine; Triau, Stéphane; Savagner, Frédérique; Malthièry, Yves

doi:10.1038/sj.bjc.6605111

Cited by 34 publications

(24 citation statements)

References 44 publications

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“…DAP3 was found to be overexpressed in human thyroid oncocytic tumours and correlated with human thymoma stage (19,20). In breast cancer, however, DAP3 was found to be lost in aggressive tumours, and low levels of DAP-3 were found to be linked to a shorter survival of breast cancer patients (20). In the present study, the DAP1 expression pattern in colorectal adenocarcinoma was similar to that of DAP2.…”

Section: Discussionsupporting

confidence: 60%

“…DAP2 has been reported to be below the limit of detection in 80% of B cell leukemia cell lines, while the frequency of loss of DAP2 expression in breast, bladder and renal carcinoma cell lines ranges from 30 to 40% (16) Promoter hypermethylation of DAP2 was also reported in various types of human tumours, including B cell lymphoma, non-small cell lung, head and neck and colon cancer (17,18). DAP3 was found to be overexpressed in human thyroid oncocytic tumours and correlated with human thymoma stage (19,20). In breast cancer, however, DAP3 was found to be lost in aggressive tumours, and low levels of DAP-3 were found to be linked to a shorter survival of breast cancer patients (20).…”

Section: Discussionmentioning

confidence: 99%

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Death associated protein 1 is correlated with the clinical outcome of patients with colorectal cancer and has a role in the regulation of cell death

Jia

et al. 2013

Oncology Reports

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Abstract. Death-associated protein 1 (DAP1) is a member of the DAP family and has been implicated in the regulation of cell growth and death including that of cancer cells. However, the roles of DAP1 in clinical cancer and in the regulation of colorectal cancer cells are largely unknown. The present study investigated the expression profile of DAP1 in human colorectal cancer and the impact of DAP1 on apoptosis and the cellular response to 5-FU. Human colorectal cancer specimens (n=94) and human colorectal cancer cell lines HRT18 and HT115 were used. DAP1 transcript and protein were evaluated using quantitative transcript analysis and immunohistochemistry. DAP1-knockdown cells were generated using anti-DAP1 transgene. The results revealed that human colorectal cancer tissues had lower levels of DAP1 when compared with the normal tissues. The reduced levels were associated with higher Dukes' stage and lymph node metastasis. Patients with low DAP1 expression had a markedly reduced survival. Loss of DAP1 in colorectal cancer cells resulted in a gain in cellular migration and loss of their sensitivity of apoptosis to chemotherapeutic agent, 5-FU. DAP1 was found to be correlated with disease progression and long-term survival of the colorectal patients. DAP1 is also a pivotal regulator of the growth and apoptosis and cellular response to chemotherapy agents. IntroductionDAP1 is one of the members of the death-associated protein (DAP) family, first isolated as a gene involved in IFN-γ-induced apoptosis through a technical knockout strategy (TKO), i.e. random inactivation of genes with antisense cDNA libraries (1). The DAP family is comprised of DAP1, DAP2 (DAP kinase), DAP3, DAP4 and DAP5. DAP2 was found to be involved in apoptosis induced by IFN-γ, TNF-α and Fas (2-3). Serine/threonine kinase catalytic activity and the death domain contribute to the pro-apoptotic function. Based on the loss of DAP2 expression in certain types of cancers, it has been proposed as a candidate tumour-suppressor gene. While the clinical significance of other members of the DAP Family that also exhibit death-promoting functions remain largely unknown, there have been recent reports on the possible association between the DAP family and the clinical outcome of patients with malignant diseases, for example breast cancer (4).Induction of apoptosis is an important mechanism of chemotherapeutic agents in the treatment of cancer. Among the DAP family members, DAP3 was found to be a mitochondrial protein that has a specific amino acid sequence to recognise and anchor to mitochondria. Mitochondria play a key role in apoptosis including release of pro-apoptotic substances such as cytochrome c and AIF, production of reactive oxygen species (ROS) and reduction in ATP synthesis (5-8). All of these findings indicate that DAP may be involved in both the intrinsic and extrinsic apoptosis pathways. In addition, it was reported that DAP2 methylation is associated with a reduced response to chemotherapy and poor prognosis in gastric cancer (9).In the present...

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Death associated protein 1 is correlated with the clinical outcome of patients with colorectal cancer and has a role in the regulation of cell death

Jia

et al. 2013

Oncology Reports

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“…It would be interesting to compare these results with those obtained in non-Hürthle cell tumors to evaluate the specificity of the data. Death-associated protein 3 (DAP3), a GTP-binding constituent of the small subunit of the mitochondrial ribosome with a proapoptotic function, was found overexpressed in Hürthle cell FTC (Jacques et al 2009). The authors studied 61 normal thyroids and 100 cases of different thyroid tumor histotypes, by tissue array, and found that DAP3 was overexpressed in 7/9 Hürthle cell FTC, 26/37 Hürthle cell FTA and in 16/34 PTCs, being absent in 2/4 PDTCs, 5/5 FTCs, 3/3 tumors of uncertain malignancy potential, and 8/8 FTA.…”

Section: R136mentioning

confidence: 99%

“…The authors studied 61 normal thyroids and 100 cases of different thyroid tumor histotypes, by tissue array, and found that DAP3 was overexpressed in 7/9 Hürthle cell FTC, 26/37 Hürthle cell FTA and in 16/34 PTCs, being absent in 2/4 PDTCs, 5/5 FTCs, 3/3 tumors of uncertain malignancy potential, and 8/8 FTA. It was concluded that DAP3 overexpression appears to be dependent on the cell mitochondrial content, suggesting that DAP3 may be necessary for an increased mitochondrial biogenesis, regulating the mitochondrial protein synthesis (Jacques et al 2009). …”

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

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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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“…Recently, overexpression of death-associated protein 3 (DAP3) was reported in oncocytic thyroid tumors [27]. DAP3 is a GTP-binding constituent of the small subunit of the mitochondrial ribosome with proapoptotic function and participates in maintaining mitochondrial homeostasis [27].…”

Section: Molecular Basis Of Oncocytic Changementioning

confidence: 99%

Oncocytes, Oxyphils, Hürthle, and Askanazy Cells: Morphological and Molecular Features Of Oncocytic Thyroid Nodules

Mete

Sylvia

2009

Endocr Pathol

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Our understanding of oncocytic change in thyroid nodules is evaluated in light of the recent progress in understanding the mitochondrial DNA, its mutations, and somatic mutations that affect mitochondrial function. These changes are largely unrelated to the genetic events that result in proliferation and neoplastic transformation of thyroid follicular epithelial cells. The criteria for diagnosing lesions that are composed predominantly of oncocytic cells are the same as those applied to follicular lesions that do not contain oncocytic cells, including follicular variant papillary carcinomas, based on nuclear morphology, immunohistochemical profiles, and molecular markers.

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

Cited by 34 publications

References 44 publications

Death associated protein 1 is correlated with the clinical outcome of patients with colorectal cancer and has a role in the regulation of cell death

Death associated protein 1 is correlated with the clinical outcome of patients with colorectal cancer and has a role in the regulation of cell death

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

Oncocytes, Oxyphils, Hürthle, and Askanazy Cells: Morphological and Molecular Features Of Oncocytic Thyroid Nodules

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