Adenovirus-mediated antisense expression of telomerase template RNA induces apoptosis in lung cancer cells

Abstract

Telomerase is a ribonucleoprotein complex, whose function is to add telomeric repeats (TTAGGG)(n) to chromosomal ends and is also known to play an important role in cellular immortalization. Telomerase is highly active in most tumor cells, yet not in normal cells. Therefore, it may have possible applications in cancer gene therapy. Telomerase consists of two essential components; a telomerase RNA template (hTR) and a catalytic subunit (hTERT). The current study attempted to inhibit the "open" part of the human telomerase RNA (hTR) with an antisense sequence-expressing adenovirus. It was found that the antisense telomerase adenovirus suppressed the telomerase activity, tumor cell growth, and survival in vitro. Furthermore, FACS analysis and TUNEL assay suggested that the reduced viability was mediated through the induction of apoptosis, indicating that this approach might be a useful method for suppressing cancer growth in targeted cancer gene therapy.