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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4313-4318
NEOPLASIA
Interferon  down-regulates telomerase reverse transcriptase
and telomerase activity in human malignant and nonmalignant
hematopoietic cells
Dawei Xu,
Sven Erickson,
Michael Szeps,
Astrid Gruber,
Olle Sangfelt,
Stefan Einhorn,
Pavel Pisa, and
Dan Grandér
From the Department of Medicine, Division of Hematology
and Department of Oncology-Pathology, Radiumhemmet Karolinska Hospital,
Stockholm, Sweden.
Recently, the derepressed expression of the catalytic subunit
of telomerase, human telomerase reverse transcriptase (hTERT), the
enzyme that elongates telomeres, has been implicated as an important
step in the immortalization process. The exact regulation of hTERT
expression, which is the rate-limiting factor for telomerase activity,
is at present unclear. As transformed cells seem to be dependent on a
constitutive telomerase activity, the availability of inhibitors would
potentially be of great value in antineoplastic therapy. Interferons
(IFNs) have been successfully used in the treatment of several forms of
malignancies, but the underlying molecular mechanisms responsible for
the antitumor activity are poorly defined. In this study we have
investigated the effects of IFNs on hTERT expression and telomerase
activity. We found that IFN- rapidly (commonly within 4 hours) and
significantly down-regulates the expression of hTERT and telomerase
activity in a number of human malignant hematopoietic cell lines,
primary leukemic cells from patients with acute leukemia as well as
T-lymphocytes from healthy donors. This effect of IFN- did not seem
to depend on IFN--mediated cell growth arrest or alterations in
c-myc expression. The finding that IFN induces a repression of hTERT
and a decrease in telomerase activity suggests a novel mechanism that
may play a significant role in the antitumor action of IFN.
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