Telomerase enzyme activity and RNA expression in adriamycin-resistant human breast carcinoma MCF-7 cells.
Telomerase activity has been reported in cancer cells after treatment with antineoplastic agents. Assessment of telomerase activity could be a valuable tool to measure the reduction of aggression caused by chemotherapy. This study was designed to investigate the significance of telomerase for chemotherapy with respect to Adriamycin (ADM)-resistance. MCF-7 and its ADM-resistant line (AdrR) were treated with ADM, 5-fluorouracil (5FU) or taxotere (TAXO). Telomerase activity and human telomerase RNA component (hTR) were quantitatively measured by the telomeric repeat amplification protocol assay and RT-PCR, respectively. Cell counting and MTT assay were also performed. In MCF-7, enzyme activity was significantly reduced by ADM and 5FU treatments. In AdrR, 5FU and TAXO reduced enzyme activity, while ADM significantly increased the activity. No significant changes in hTR were seen in these two cell lines after treatment with any of these drugs. When Bcl-2 expression was examined after drug treatments, ADM increased Bcl-2 expression in AdrR cells, while not changing it in MCF-7 cells. We conclude that an unusual reaction of telomerase activity in AdrR may explain, at least in part, one of the mechanisms of the malignant biological behavior related with the drug-resistance to ADM.
Ishikawa
T
T
Second Department of Surgery, Yokohama City University, Yokohama, Japan.
Kamiyama
M
M
Hisatomi
H
H
Ichikawa
Y
Y
Momiyama
N
N
Hamaguchi
Y
Y
Hasegawa
S
S
Narita
T
T
Shimada
H
H
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D002277:Carcinoma / Q000201:enzymology* / Q000378:metabolism; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004587:Electrophoresis, Agar Gel; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D043823:Taxoids; D019098:Telomerase / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D043823:Taxoids; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077143:Docetaxel; D004317:Doxorubicin; D019098:Telomerase; C022616:thiazolyl blue; D017239:Paclitaxel; D005472:Fluorouracil