Telomerase reverse transcriptase promotes the proliferation of human laryngeal carcinoma cells through activation of the activator protein 1.
TERT is the main functional unit of telomerase, which maintains telomere length and chromosome structure stability. TERT has been shown to act as a key factor in various biological processes, such as cell proliferation, via uncharacterized mechanisms. We transfected HEp-2 laryngeal carcinoma cells with a TERT overexpressing adenovirus (Ad-TERT) and TERT shRNA silencing adenovirus (Ad-sh-TERT), and examined the effect on TERT and the AP-1 transcription factor subunits c-Fos and c-Jun using RT-PCR and western blot analysis.TERTmRNA expression was quantified using RT-PCR in 24 human laryngeal carcinoma samples, and TERT protein co-expression with AP-1 was investigated in a human laryngeal carcinoma tissue microarray using quantum-dot based immunofluorescence. The effect of specific ERK and p38 inhibitors on ERK, p38, c-Jun and c-Fos phosphorylation was investigated in TERT-overexpressing HEp-2 cells. TERT overexpression led to increased TERT, c-Jun and c-Fos mRNA and protein expression and increased cell proliferation, while TERT silencing had the opposite effects.TERTmRNA expression levels were positively correlated withc-Fosandc-JunmRNA in human laryngeal carcinoma tissue. TERT and AP-1 protein were expressed at high levels and positively correlated in laryngeal carcinoma tissues. Treatment of TERT-overexpressing HEp-2 cells with specific p38 and ERK inhibitors indicated that TERT modulates the expression and phosphorylation of the AP-1 subunits c-Jun and c-Fos through the p38 and ERK signaling pathways. In conclusion, the results of this study indicate that TERT is capable of promoting cell proliferation via activation of the AP-1 subunits, c-Jun and c-Fos, in laryngeal carcinoma cells.
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China.
Yang
Y
Jiang
Chen
C
Chen
Shi-Ming
SM
Chen
Ya-Qiu
YQ
Wang
Yong
Y
Xu
Yan
Y
Wang
Zhe
Z
Chen
Bo-Kui
BK
Xiao
Ze-Zhang
ZZ
Tao
activator protein 1; extracellular regulated protein kinase; laryngeal carcinoma; p38; telomerase reverse transcriptase