Telomerase activity in myeloma cells is closely related to cell cycle status, but not to apoptotic signals induced by interferon-alpha.
Telomeres, G-rich structures at the ends of chromosomes are essential for maintaining chromosomal integrity. Most tumor cells contain telomerase, a ribonucleoprotein that elongates telomeric repeats, and it plays an essential role in indefinite proliferation. To better understand regulatory mechanisms of telomerase, in relationship with apoptosis and the cell cycle, we examined telomerase activity in PCM6, an interleukin-6 (IL-6)-responsive, interferon-alpha (IFN-alpha)-sensitive multiple myeloma cell line, using a PCR-based assay. When PCM6 cells were cultured in serum-free media, the addition of IFN-alpha resulted in apoptosis of the cells, but with no influence on telomerase activity. When IFN-alpha was added to the culture with serum plus rIL-6 after serum deprivation, G1-S transition was inhibited and telomerase activity was lower compare to findings in culture with no IFN-alpha. Dose response experiments of rIL-6 and IFN-alpha, and the measurement of telomerase activity of sorted cells in S-phase using CD71, demonstrated a higher activity of telomerase in the samples which contained a larger proportion of cells in S-phase. These data indicate that regulation of telomerase activity is closely related to cell cycle status, in particular cells in S-phase have an high telomerase activity. While telomeres play an important role in cellular senescence, the regulation of telomerase is independent from apoptotic signals induced by IFN-alpha in myeloma cells.
Shiratsuchi
M
M
Third Department of Internal Medicine, Kyushu University, Fukuoka, Japan. shira@intmed3.med.kyushu-u.ac.jp
Muta
K
K
Umemura
T
T
Nishimura
J
J
Nawata
H
H
Kozuru
M
M
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D016898:Interferon-alpha; D019098:Telomerase