Up-regulation of human telomerase catalytic subunit during gastric carcinogenesis

BACKGROUND. Telomerase activation is thought to be essential for the stabil ization of telomere length, through which immortalization and oncogenesis a re achieved, but little is known about the regulation of telomerase in huma n gastric carcinoma cells. METHODS. A total of 27 primary gastric tumors, 29 cases of intestinal metap lasia, and 30 cases of normal mucosa, as well as 8 gastric carcinoma cell l ines, were examined for the relation between telomerase activation and gast ric carcinogenesis. Telomerase activity was detected by telomeric repeat am plification protocol, and the expression of each telomerase subunit was eva luated by Northern blot analysis or reverse transcriptase-polymerase chain reaction. RESULTS, Telomerase activity was found in all 8 gastric carcinoma cell line s and in 25 of 27 gastric carcinoma tissue samples (93%), and weakly observ ed in 11 of 29 gastric intestinal metaplasia samples (38%). None of 30 norm al gastric tissue samples displayed telomerase activity. The mRNA expressio n of human telomerase catalytic subunit (hTERT) was up-regulated in 26 of 2 6 tumor tissue samples (100%) and in 19 of 24 intestinal metaplasia (79%) i n which telomerase activity was weak or negative. Normal gastric mucosa exp ressed the telomerase gene, albeit at low levels. In contrast to hTERT, hum an telomerase RNA component and human telomerase-associated protein express ion did not parallel telomerase activity, which was independent of tumor st age and histology. CONCLUSIONS. hTERT expression is up-regulated during an early stage in the carcinogenic process, and telomerase activation may be a critical step in g astric carcinogenesis. Cancer 1999;86:559-65. (C) 1999 American Cancer Soci ety.