TELOMERE LENGTH, TELOMERASE ACTIVITY AND TELOMERASE RNA EXPRESSION INHUMAN ESOPHAGEAL CANCER-CELLS - CORRELATION WITH CELL-PROLIFERATION, DIFFERENTIATION AND CHEMOSENSITIVITY TO ANTICANCER DRUGS

The telomere and the enzyme telomerase in esophageal cancer have been poorly investigated. We present here aspects of the telomere and telom erase in esophageal cancer in I elation to cell proliferation, differe ntiation and chemosensitivity to anticancer drugs. The telomere length (mean length of telomere restriction fragments; TRF), telomerase acti vity (TA), and human telomerase RNA (hTR) expression in a panel of 13 human esophageal cancer cell lines, squamous in origin, was examined b y Southern blotting, the telomeric repeat amplification protocol (TRAP ), and reverse transcriptase-polymerase chain reaction (RT-PCR), respe ctively. Cell proliferation expressed by the doubling time, cell diffe rentiation determined by the keratin 13 and/or 14 expression,,and chem osensitivity to cisplatin (CDDP) and 5-fluorouracil (5-FU) were compar ed with telomere-related factors. TRF shortening, the up-regulation of TA, and hTR expression was seen in all 13 cell lines. The TA correlat ed positively with the telomere length and negatively with the hTR exp ression. The doubling times of the cell lines and the telomere-related factors did not show any significant relation. The TA in the keratin 13/14-negative cell lines was significantly higher than that of the ke ratin W-positive cell lines. The cells with short telomere tended to b e resistant to CDDP whereas the cells with higher TA tended to be mole sensitive to CDDP; 5-FU showed no relation to any telomere-related fa ctors. Therefore, the activation of TA in esophageal squamous cell car cinoma is regulated by cell differentiation but nor by cell proliferat ion, cells with high TA are more sensitive to CDDP, and cells with sho rt telomere require a CDDP dose escalation.