Methylation status of the PTEN gene in adenoid cystic carcinoma cells

Fan, Xiaoping; Chen, Bin; Xu, Junli; Zhang, Huachang; Deng, Feng; Xiang, Xue-Rong

doi:10.3892/mmr.2010.337

Cited by 5 publications

(2 citation statements)

References 10 publications

(11 reference statements)

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“…In contrast, either homozygous or hemizygous deletion of PTEN has been reported in over 20% of human SGTs and correlated with PTEN expression [ 9 ]. The results of PTEN methylation in human SGTs are controversial and inconclusive [ 20 , 21 ]. In addition to these genetic or epigenetic changes, posttranslational modification or certain microRNAs targeting PTEN are also possible to be responsible for the reduced expression of PTEN in human SGTs.…”

Section: Discussionmentioning

confidence: 99%

High frequency of loss of PTEN expression in human solid salivary adenoid cystic carcinoma and its implication for targeted therapy

Liu

Wang

et al. 2015

Oncotarget

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Salivary gland tumor (SGT) is one of the least studied cancers due to its rarity and heterogeneous histological types. Here, we reported that loss of PTEN expression was most frequently found in the poorly differentiated, high grade solid adenoid cystic carcinomas. Loss of PTEN expression correlated with activation of mTOR by increased phosphorylated S6 ribosome protein. We further functionally studied the role of PTEN in a pair of human SACC cell lines, SACC-83 and SACC-LM. Reduced PTEN level was correlated with the metastasis potential. When we knocked down PTEN in the SACC-83 cell line, we observed increased proliferation and enhanced migration/invasion in vitro, and increased tumor size in vivo. We further tested the therapeutical effect by applying a PI3K/mTOR inhibitor NVP-BEZ235 to both SACC cell lines. Decreased cell proliferation, increased apoptosis, as well as reduced cell migration/invasion were observed in both cell lines upon the NVP-BEZ235 treatment. Moreover, the NVP-BEZ235 treatment in a SGT xenograft mouse model significantly reduced primary tumor size and lung metastasis. Taken together, our results demonstrated that PTEN is a potent tumor suppressor in human SGTs, and targeting PI3K/mTOR pathway may be effective in the targeted therapy for human SGT patients with loss of PTEN expression.

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Section: Discussionmentioning

confidence: 99%

High frequency of loss of PTEN expression in human solid salivary adenoid cystic carcinoma and its implication for targeted therapy

Liu

Wang

et al. 2015

Oncotarget

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“…Hypomethylation of oncogenes can result in aberrant activation, and hypermethylation of suppressor genes can lead to silencing. Several methylation-regulated candidate genes have been identified in SACC, including auprabasin (SBSN) ( 12 ), aquaporin 1 (AQP1) ( 13 ), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) ( 14 ), cyclin-dependent kinase inhibitors ( 15 ), RAS-associated domain family protein 1A (RASSF1) ( 16 ), and death-associated protein kinase (DAPK) ( 17 ), but the methylation of RECK in SACC has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Effects of 5-aza-2′deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma

Zhou

Huang

Zhang

et al. 2015

Braz J Med Biol Res

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Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2′deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.

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Current understanding of adenoid cystic carcinoma in the gene expression and targeted therapy

et al. 2023

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Adenoid Cystic Carcinoma (ACC) has been considered as a "quiet" tumor. It is typically malignancy arising from exocrine glands with poor long-term prognosis due to high rate of recurrence and distant metastasis. It is characterized by perineural infiltration, distant metastasis, and positive incision edge. Surgery is the first line treatment for ACC, followed by cytotoxic chemotherapy and/or radiotherapy as adjuvant treatments to avoid recurrence. But recurrence or metastasis still occurs in more than 50% ACC. Recurrent and/or metastasis (R/M) ACC is usually incurable, and no systemic agent has been found effective. With the widespread use of whole exome sequencing (WES) and whole genome sequencing (WGS), its internal oncogenic mechanism is gradually revealed, which involving molecular mutations such as the MYB family gene translocation, Notch signal pathway, DNA damage repair (DDR) pathway and epigenetic molecular mutations. The review helps us to understand the linkage among the pathways and targeted genes in diagnosis and related treatment of ACC till now.

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Methylation status of the PTEN gene in adenoid cystic carcinoma cells

Cited by 5 publications

References 10 publications

High frequency of loss of PTEN expression in human solid salivary adenoid cystic carcinoma and its implication for targeted therapy

High frequency of loss of PTEN expression in human solid salivary adenoid cystic carcinoma and its implication for targeted therapy

Effects of 5-aza-2′deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma

Current understanding of adenoid cystic carcinoma in the gene expression and targeted therapy

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