Telomerase activity and telomere length in human ovarian cancer and melanoma cell lines: correlation with sensitivity to DNA damaging agents.
Since telomerase plays a role in cellular resistance to apoptosis, which is the primary mode of cell death induced by several drugs, telomerase could be involved in determining the chemosensitivity profile of tumor cells. Thus, we investigated the relationship between telomerase activity, telomere length and chemosensitivity to effective antitumor agents in a panel of human melanoma and ovarian cancer cell lines. Telomerase activity, as detected by the telomeric repeat amplification protocol, ranged from 0.58 to 1.10 arbitrary units in individual cell lines, with similar median values for melanoma and ovarian carcinoma cell lines (0.80 vs. 0.90). Telomeres were generally longer in melanoma than in ovarian carcinoma cell lines, with a more than 2-fold median telomere restriction fragment length (7.74 vs. 3.82 kb). No significant correlation was evidenced between the two telomere-related parameters and cell population doubling time, DNA index or TP53 gene status. No precise relation was found between telomerase activity and cellular sensitivity to different DNA damaging agents including doxorubicin, cisplatin and the multinuclear platinum compound BBR 3464. In contrast, longer telomeres were associated to resistance to the drugs, even though the association reached statistical significance only for cisplatin. Since platinum compounds may have affinity for telomere sequences, it is conceivable that the interaction is relevant for drug sensitivity/resistance status depending on telomere length.
Villa
R
R
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Folini
M
M
Perego
P
P
Supino
R
R
Setti
E
E
Daidone
M G
MG
Zunino
F
F
Zaffaroni
N
N
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000648:ultrastructure*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000648:ultrastructure*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D019098:Telomerase