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Up‐regulation of human telomerase catalytic subunit during gastric carcinogenesis
Author(s) -
Jong HyunSoon,
Park Young I.,
Kim Sung,
Sohn Jin H.,
Kang Shin H.,
Song Sang H.,
Bang YungJue,
Kim Noe K.
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990815)86:4<559::aid-cncr3>3.0.co;2-4
Subject(s) - telomerase , telomerase reverse transcriptase , carcinogenesis , intestinal metaplasia , telomere , protein subunit , cancer research , biology , gastric mucosa , microbiology and biotechnology , cancer , pathology , medicine , stomach , gene , genetics , biochemistry
BACKGROUND Telomerase activation is thought to be essential for the stabilization of telomere length, through which immortalization and oncogenesis are achieved, but little is known about the regulation of telomerase in human gastric carcinoma cells. METHODS A total of 27 primary gastric tumors, 29 cases of intestinal metaplasia, and 30 cases of normal mucosa, as well as 8 gastric carcinoma cell lines, were examined for the relation between telomerase activation and gastric carcinogenesis. Telomerase activity was detected by telomeric repeat amplification protocol, and the expression of each telomerase subunit was evaluated by Northern blot analysis or reverse transcriptase–‐polymerase chain reaction. RESULTS Telomerase activity was found in all 8 gastric carcinoma cell lines and in 25 of 27 gastric carcinoma tissue samples (93%), and weakly observed in 11 of 29 gastric intestinal metaplasia samples (38%). None of 30 normal gastric tissue samples displayed telomerase activity. The mRNA expression of human telomerase catalytic subunit (hTERT) was up‐regulated in 26 of 26 tumor tissue samples (100%) and in 19 of 24 intestinal metaplasia (79%) in which telomerase activity was weak or negative. Normal gastric mucosa expressed the telomerase gene, albeit at low levels. In contrast to hTERT, human telomerase RNA component and human telomerase‐associated protein expression did not parallel telomerase activity, which was independent of tumor stage 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 gastric carcinogenesis. Cancer 1999;86:559–65. © 1999 American Cancer Society.