Jeung Hei Cheul, Rha Sun Young, Shin Sang Joon, Ahn Joong Bae, Park Kyu Hyun, Kim Tae Soo, Kim Jin Ju, Roh Jae Kyung, Chung Hyun Cheol
Cancer Metastasis Research Center, Division of Medical Oncology, Cancer Center Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea.
Cancer Metastasis Research Center, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Oncol Lett. 2017 Aug;14(2):2385-2392. doi: 10.3892/ol.2017.6438. Epub 2017 Jun 21.
Human telomerase reverse transcriptase (hTERT) expression level may not always correlate with telomerase activity. The present study analyzed hTERT splicing patterns with respect to hTERT and telomerase activity in colorectal cancer. Telomerase activity was determined by telomeric repeat amplification protocol assay, and spliced variants of hTERT were identified by reverse transcription-polymerase chain reaction in 40 colorectal cancer tissue samples. In the lower range of telomerase activity (0-100 units), the percentage of the β variant decreased with the increment in telomerase activity, whereas in the higher range of telomerase activity (>100 units), total hTERT expression level revealed a trend toward increment. There was a positive correlation between the full-length variant level and β variant level. Conversely, there was a negative correlation between the percentage of the full-length variant and β variant. Tumor-node-metastasis stage was the strongest prognostic factor in multivariate analysis and the percentage of the full-length variant was an independent prognostic factor for survival. Telomerase activity was primarily altered with changes in alternative splicing of the full-length and β variants of hTERT in colorectal cancer.
人端粒酶逆转录酶(hTERT)的表达水平可能并不总是与端粒酶活性相关。本研究分析了结直肠癌中hTERT剪接模式与hTERT及端粒酶活性的关系。通过端粒重复序列扩增法检测端粒酶活性,并采用逆转录-聚合酶链反应在40例结直肠癌组织样本中鉴定hTERT的剪接变体。在端粒酶活性较低范围(0 - 100单位)内,β变体的百分比随端粒酶活性增加而降低,而在端粒酶活性较高范围(>100单位)内,hTERT总表达水平呈上升趋势。全长变体水平与β变体水平呈正相关。相反,全长变体百分比与β变体百分比呈负相关。在多因素分析中,肿瘤-淋巴结-转移分期是最强的预后因素,全长变体百分比是生存的独立预后因素。在结直肠癌中,端粒酶活性主要随hTERT全长和β变体的可变剪接变化而改变。