Cd. Belair et al., TELOMERASE ACTIVITY - A BIOMARKER OF CELL-PROLIFERATION, NOT MALIGNANT TRANSFORMATION, Proceedings of the National Academy of Sciences of the United Statesof America, 94(25), 1997, pp. 13677-13682
Telomerase activity is readily detected in most cancer biopsies, but n
ot in premalignant lesions or in normal tissue samples with a few exce
ptions that include germ cells and hemopoietic stem cells. Telomerase
activity may, therefore, be a useful biomarker for diagnosis of malign
ancies and a target for inactivation in chemotherapy or gene therapy.
These observations have led to the hypothesis that activation of telom
erase may be an important step in tumorigenesis. To test this hypothes
is, we studied telomerase activity In Isogeneic samples of uncultured
and cultured specimens of normal human uroepithelial cells (HUCs) and
in uncultured and cultured biopsies of superficial and myoinvasive tra
nsitional cell carcinoma (TCC) of the bladder. Our results demonstrate
d that four of four TCC biopsies, representing both superficial and my
oinvasive TCCs, were positive for telomerase activity, but all samples
of uncultured HUC were telomerase negative. However, when the same no
rmal HUC samples were established as proliferating cultures in vitro,
telomerase activity was readily detected but usually al lower levels t
han in TCCs. Consistent with the above observation of the telomerase a
ctivity in HUCs, telomeres did not shorten during the HUC in vitro lif
espan. Demonstration of telomerase In proliferating human epithelial c
ells in vitro was not restricted to HUCs, because it was also present
in prostate and mammary cell cultures. Notably, telomerase activity wa
s relatively low or undetectable in nonproliferating HUC cultures. The
se data do not support a model in which telomerase is inactive in norm
al cells and activated during tumorigenic transformation. Rather, thes
e data support a model In which the detection of telomerase in TCC bio
psies, but not uncultured HUC samples, reflects differences in prolife
ration between tumor and normal cells in vivo.