Methylthioadenosine phosphorylase inactivation depends on gene deletion in laryngeal squamous cell carcinoma

Conde, Laura; Vilaseca, Isabel; Alós, Llúcia; Bernal‐Sprekelsen, Manuel; Cardesa, Antonio; Nadal, Alfons

doi:10.1111/j.1365-2559.2012.04353.x

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…MTAP loss can be associated with CDKN2A loss [ 10 – 12 , 25 ], and promoter hypermethylation has been described as an alternative mechanism for the loss of MTAP expression [ 26 ]. Here, we characterized gene expression (mRNA and protein levels) of MTAP and CDKN2A in seven breast cancer cell lines and performed a promoter methylation analysis of MTAP ( Fig 3 , Table 2 and S1 Fig ).…”

Section: Discussionmentioning

confidence: 99%

Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines

et al. 2016

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MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors´ MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNBC.

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Section: Discussionmentioning

confidence: 99%

Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines

et al. 2016

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“…The correlation between MTAP deletion and loss of expression has been found in multiple types of cancers, including gastrointestinal stromal tumors, 28 laryngeal squamous cell carcinoma, 29 and glioblastoma multiforme. 30 In the present study, we established a significantly positive correlation between copy number and mRNA level of MTAP in ESCC.…”

Section: Discussionmentioning

confidence: 99%

Deletion and downregulation of MTAP contribute to the motility of esophageal squamous carcinoma cells

Xiaoyu¹,

Liu²,

Li³

et al. 2017

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Esophageal squamous cell carcinoma (ESCC) is among the most common malignancies, with a low 5-year overall survival rate. In previous studies, we and others have found that 9p21.3 was the most frequently deleted region in ESCC. The MTAP gene, which is located close to CDKN2A/B in 9p21.3, encodes methylthioadenosine phosphorylase. This enzyme plays an important role during the process of adenosine transfer. In the present study, we found that MTAP is deleted at the genomic level in 19.1% (64/341) of primary ESCC tumors, and decreased mRNA and protein expression were present in 31.1% (28/90) and 33.3% (6/18) of ESCCs, respectively. Further statistical analysis showed a positive correlation between deletion and decreased mRNA expression of MTAP in the ESCC tissues tested (coefficient: 0.826; P=1.17×10−23). Knockdown of MTAP expression using small interfering RNA-mediated silencing promoted the invasion and migration of ESCC cells. Also, overexpression of MATP using pcDNA3.1-MTAP plasmid decreased the cell invasion and migration. At the molecular level, MTAP knockdown downregulated E-cadherin and p-GSK3β but upregulated Slug expression. Our results indicated that MTAP deletion results in the decreased expression in ESCCs and that it plays a role in promoting the mobility and inducing the epithelial-to-mesenchymal transition of ESCC cells via the GSK3β/Slug/E-cadherin axis. The data suggest that MTAP might function as a tumor suppressor gene in ESCC.

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Development of head and neck pathology in Europe

et al. 2022

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Methylthioadenosine phosphorylase inactivation depends on gene deletion in laryngeal squamous cell carcinoma

Cited by 3 publications

References 26 publications

Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines

Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines

Deletion and downregulation of MTAP contribute to the motility of esophageal squamous carcinoma cells

Development of head and neck pathology in Europe

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