INCREASED EXPRESSION OF TELOMERASE RNA COMPONENT IS ASSOCIATED WITH INCREASED CELL-PROLIFERATION IN HUMAN ASTROCYTOMAS

Deregulation of telomerase, a ribonucleoprotein polymerase that compen sates progressive loss of telomeric (TTAGGG)n repeats during DNA repli cation, has been suggested to facilitate tumorigenesis and cellular im mortality by providing unlimited proliferation capacity for cancer cel ls, We investigated the relationship between tumor proliferation activ ity and in situ expression of the telomerase RNA component in 46 human grade I to IV astrocytomas. Heterogeneously distributed telomerase RN A expression was detected from all of the tumor samples as well as fro m normal human brain tissue However, expression of telomerase RNA was significantly increased in highly malignant tumors (P = 0.024) and in tumors that showed increased proliferation activity determined by MIB- 1 immunohistochemistry (P = 0.014). Interestingly, increased telomeras e RNA levels were observed in a subgroup of grade II astrocytomas that showed significant increase in proliferation activity (P = 0.047), in dicating that the telomerase RNA component is up-regulated already in early states of astrocytoma malignancy, Telomeric repeats amplificatio n assays revealed telomerase activity in 4 of 6 glioblastomas and in I rapidly proliferating grade II astrocytoma. These results suggest tha t increased tumor proliferation activity triggers telomerase activatio n via mechanisms that involve increased production of the telomerase R NA component.