Modulation of telomere shelterin by TRF1 [corrected] and TRF2 interacts with telomerase to maintain the telomere length in non-small cell lung cancer.
Our previous report demonstrated good correlations between the expressions of h-TERT and its associated genes, such as c-Myc, TRF1 and TRF2. To observe the interaction between telomerase activity and expression of its associated genes in regulation of the telomere restriction fragment length (TRFL) in non-small cell lung cancer (NSCLC), 79 NSCLC specimens were examined. Telomerase activity, h-TERT, TRF1 and TRF2 genes expression were observed in 60.8, 66.7, 74.7, and 83.5% of the tumour tissues, respectively. The TRFL were shorter in both tumour tissues and telomerase positive tissues, as compared to their counterparts. The t/n-TRFLR (tumour-to-normal TRFL ratio) was also lower in telomerase positive tissues. When telomerase was negative, the t/n-TRFLR was lower in both TRF1 positive and TFR2 positive. However, when telomerase was positive, the t/n-TRFLR was only lower in the TFR2 positive group. When t/n-TRFLR level was equal to or less than 75%, the majority of the specimens became TRF1 and TRF2 positive. To explain these findings, our hypothesis is that when the TRF length becomes shorter during tumour progression, the tumour cells can sustain a better tolerance to shorter telomere with the help of both TRF1 and TRF2, but without immediate activation of the telomerase. However, when the TRF length reaches a critical level, changing the telomere shelterin by persistent expression of the TRF2, which in combination with telomerase activation reverses the telomere shortening.
Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. cliff@vghtc.gov.tw
Chung-Ping
CP
Hsu
Jiunn-Liang
JL
Ko
Sen-Ei
SE
Shai
Li-Wen
LW
Lee
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000378:metabolism*; D000089804:Shelterin Complex; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*
D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2; C509186:TERT protein, human; D019098:Telomerase