Department of Oral Biology Faculty of Dentistry, Mahidol University 6 Yothi Street, Bangkok, Thailand
Med Oral Patol Oral Cir Bucal. 2020 Jul 1;25(4):e481-e487. doi: 10.4317/medoral.23498.
Phosphatase and tensin homolog (PTEN) acts as a tumor suppressor gene. Inactivation of PTEN has been reported in various types of cancers. PTEN promoter methylation possibly underlies PTEN inactivation, which results in tumorigenesis. The aim of this study was to investigate whether PTEN promoter methylation contributes to PTEN inactivation in ameloblastoma and its associated protein expression.
In total, 20 fresh-frozen ameloblastoma samples were evaluated for PTEN promoter methylation using methylation-specific polymerase chain reaction (MS-PCR). A subset of 10 paraffin-embedded ameloblastoma samples was examined for PTEN expression through immunohistochemistry. Four primary cultured ameloblastoma cells were investigated for PTEN promoter methylation and PTEN transcriptional expression via reverse transcription PCR.
PTEN promoter methylation was detected in 65% (13/20) of the ameloblastoma samples. Of 10 ameloblastoma samples, 4 exhibited reduced PTEN expression. Of 5 samples with methylated PTEN, 3 (60%) were associated with loss of PTEN expression. However, PTEN expression was detected in 4 (80%) of 5 samples with unmethylated PTEN. In addition, 3 (75%) of 4 primary ameloblastoma cell cultures exhibited an inverse correlation between PTEN promoter methylation and PTEN transcription level.
PTEN promoter methylation is found in a number of ameloblastomas but not significantly correlated with loss of PTEN expression. Genetic or epigenetic mechanisms other than PTEN promoter methylation may contribute to PTEN inactivation in ameloblastoma tumor cells.
磷酸酶与张力蛋白同源物（PTEN）作为一种肿瘤抑制基因。PTEN 的失活已在多种类型的癌症中报道。PTEN 启动子甲基化可能导致 PTEN 失活，从而导致肿瘤发生。本研究旨在探讨 PTEN 启动子甲基化是否导致成釉细胞瘤中 PTEN 的失活及其相关蛋白表达。
共评估了 20 例新鲜冷冻成釉细胞瘤样本的 PTEN 启动子甲基化情况，采用甲基化特异性聚合酶链反应（MS-PCR）。通过免疫组织化学方法检测了 10 例石蜡包埋成釉细胞瘤样本的 PTEN 表达情况。通过逆转录聚合酶链反应（RT-PCR）检测了 4 例原代培养的成釉细胞瘤细胞的 PTEN 启动子甲基化和 PTEN 转录表达。
65%（13/20）的成釉细胞瘤样本中检测到 PTEN 启动子甲基化。在 10 例成釉细胞瘤样本中，4 例显示 PTEN 表达减少。在 5 例甲基化的 PTEN 样本中，3 例（60%）与 PTEN 表达缺失相关。然而，在 5 例非甲基化的 PTEN 样本中，有 4 例（80%）检测到 PTEN 表达。此外，在 4 例原代成釉细胞瘤细胞培养物中，PTEN 启动子甲基化与 PTEN 转录水平之间存在反比关系。
PTEN 启动子甲基化存在于一些成釉细胞瘤中，但与 PTEN 表达缺失无显著相关性。除了 PTEN 启动子甲基化之外，其他遗传或表观遗传机制可能导致成釉细胞瘤肿瘤细胞中 PTEN 的失活。
