Concomitant underexpression of TGFBR2 and overexpression of hTERT are associated with poor prognosis in cervical cancer

Abstract

The human telomerase reverse transcriptase (hTERT) is highly expressed in a variety of tumors. The transforming growth factor beta receptor type II (TGFBR2) is a downstream protein of transforming growth factor beta (TGF-β) which suppresses telomerase activity. However, the relevance of survival to the expression of TGFBR2, hTERT or TGFBR2/hTERT has not been previously investigated in cervical cancer tissues. Our study showed that patients with low level of TGFBR2 were associated with poor prognosis (HR = 1.704, P = 0.021), but no significant relevance between hTERT expression and survival (HR = 1.390, P = 0.181). However, a combination of low level of TGFBR2 and high level of hTERT was associated with a worse survival (HR = 1.892, P = 0.020), which had higher impact of hazard ratio (HR) on the overall survival (OS) than the low TGFBR2 expression alone. Knockdown of TGFBR2 expression by shRNA in Hela cells increased cell proliferation, cell invasion, G1/S transition and telomere homeostasis but decreased cell apoptosis. Overexpressing TGFBR2 and inhibiting hTERT suppressed Hela cell growth. These results would lead us to further explore whether a phenotype of TGFBR2 low/hTERT high could be considered as a predictor of poor prognosis, and whether simultaneous use of TGFBR2 agonist and hTERT inhibitor could be developed as a therapeutic strategy.