Telomerase activity in esophageal squamous cell carcinoma: down-regulation by chemotherapeutic agent.
OBJECTIVE
Telomerase has been suggested as being necessary for continued cell growth and progression of cancer. Esophageal cancer and matched normal esophageal tissue from 54 patients were analyzed for telomerase activity, human telomerase reverse transcriptase (hTERT) mRNA expression, and their correlation with clinicopathological factors.


METHODS
Telomeric repeat amplification protocol was used for detection of telomerase activity and real time quantitative RT-PCR was used for hTERT mRNA. An esophageal carcinoma cell line was used to study the effect of chemotherapeutic agent on telomerase.


RESULTS
Telomerase activity was detectable in 79.6% of the tumor and 59.3% of the normal esophageal tissue. The level of telomerase activity in the tumor was significantly higher than that in the normal tissue. A significantly higher telomerase activity was observed in tumors with extensive blood vessel invasion. A significantly lower telomerase activity was observed in tumors that showed good response to preoperative chemotherapy than those with poor response. TE-9 cells exposed to 5-FU showed a diminished telomerase activity preceded by a time-dependent decrease in the mRNA expression of hTERT.


CONCLUSIONS
Telomerase activity was high in esophageal cancer tissue and showed positive correlation with blood vessel invasion. Chemotherapeutic agents may down-regulate telomerase activity.
Mitsui
Akira
A
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. a.mitsui@med.nagoya-cu.ac.jp
Kuwabara
Yoshiyuki
Y
Iwase
Hirotaka
H
Mitani
Masami
M
Shinoda
Noriyuki
N
Sato
Atsushi
A
Toyama
Tatsuya
T
Sugiura
Masahiko
M
Suzuki
Tomotaka
T
Kato
Joji
J
Fujii
Yoshitaka
Y
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase; D005472:Fluorouracil