Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation

摘要: Telomerase, the enzyme that elongates telomeric DNA (TTAGGG)n, may be involved in cellular immortality and oncogenesis. To investigate effect of inhibition telomerase on tumor cells, we transfected antisense vector against human RNA into malignant glioma cells exhibiting activity. After 30 doublings, some subpopulations transfectants expressed a high level interleukin-1β-converting (ICE)2 protein underwent apoptosis. In contrast, other also showed enhanced ICE but escaped from apoptotic crisis continued to grow, although their synthesis, invasive ability, tumorigenicity nude mice were significantly reduced. Surviving demonstrated increased expression glial fibrillary acidic decreased motility, consistent with more differentiated state. These contained cyclin-dependent kinase inhibitors (CDKIs) p21 p27. Treatment surviving nonapoptotic w...