Expression and mechanism of PinX1 and telomerase activity in the carcinogenesis of esophageal epithelial cells
Expression and mechanism of PinX1 and telomerase activity in the carcinogenesis of esophageal epithelial cells
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DOI：
10.3892/or.2013.2649
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发表时间：
2013-10-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Zuo, Jing;Wang, Da-Hu;Liu, Wei
采用免疫组化和荧光原位杂交技术检测食管癌高发区食管组织中端粒长度和端粒酶逆转录酶（hTERT）的表达;食管癌组织，配对-从食管鳞状细胞癌手术切除标本中获得癌旁粘膜和配对的正常粘膜，以测定端粒酶活性，通过端粒重复序列扩增-银染、RT-PCR和流式细胞术（FCM）表达hTERT和Pin 2/TRF 1相互作用蛋白X1（PinX 1）。流式细胞术（FCM）和MTT法检测细胞增殖和凋亡情况。结果发现，食管上皮细胞在癌变过程中端粒DNA长度减少，hTERT蛋白表达增加;食管癌组织中端粒酶活性显著上调，PinX 1表达降低，与食管癌组织的病理分级和淋巴结转移密切相关。在Eca 109细胞中，PinX 1的过表达抑制细胞生长，使细胞停滞在G 0/G1期，并诱导细胞凋亡。此外，PinX 1过表达显著抑制端粒酶活性。结论：端粒长度缩短是食管上皮细胞癌变过程中的重要特征，其次是端粒酶活性升高和PinX 1表达下调。过表达PinX 1可抑制Eca 109细胞增殖，并通过下调端粒酶活性诱导细胞凋亡。
Esophageal tissues were collected from an esophageal carcinoma high-risk area of China and were used to detect the telomere length and the expression of human telomerase reverse transcriptase (hTERT) by immuhistochemistry and fluorescence in situ hybridization; esophageal carcinoma tissues, paired-adjacent mucosa and paired normal mucosa were obtained from resected surgical specimens of esophageal squamous cell carcinoma in order to determine telomerase activity and expression of hTERT and Pin2/TRF1 interacting protein X1 (PinX1) by telomeric repeat amplification protocol-silver staining, RT-PCR and flow cytometry (FCM). The cell proliferation and apoptosis of Eca109 cells were analyzed by FCM and MTT assay. We found that the length of telomere DNA decreased and hTERT protein expression increased in the carcinogenesis of esophageal epithelial cells; telomerase activity was significantly upregulated followed by a decrease of PinX1 expression in esophageal carcinoma compared with dysplasia and normal patients, which notably correlated with grade and lymph node metastasis. Overexpression of PinX1 inhibited cell growth, arrested cells at the G0/G1 stage and induced cell apoptosis in Eca109 cells. In addition, PinX1 overexpression significantly inhibited telomerase activity. In conclusion, the length shortening of telomere was an important characteristic in the carcinogenesis of esophageal epithelial cells, followed by increase of telomerase activity and downregulation of PinX1. Overexpression of PinX1 blocked Eca109 cell proliferation and induced cell apoptosis by downregulating telomerase activity.