Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours

被引:80
作者
Lantuejoul, S
Soria, JC
Moro-Sibilot, D
Morat, L
Veyrenc, S
Lorimier, P
Brichon, PY
Sabatier, L
Brambilla, C
Brambilla, E
机构
[1] CHU A Michallon, Serv Pathol Cellulaire, Inst A Bonniot, F-38043 Grenoble 9, France
[2] CHU Michallon, Inst A Bonniot, INSERM, U578,Lung Canc Res Grp, Grenoble, France
[3] CEA, DRR, DSV, Lab Radiol & Oncol, Fontenay Aux Roses, France
关键词
lung cancer; hTERT; telomerase; immunohistochemistry; nucleolar localization;
D O I
10.1038/sj.bjc.6601643
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Human telomerase reverse transcriptase is a ribonucleoprotein that synthesises telomeric sequences, which decrease at each cell division. In cancer cells, its activity is linked to telomere maintenance leading to unlimited cellular proliferation and immortality. To evaluate the prognostic value of the catalytic subunit telomerase reverse transcriptase (hTERT), we analysed its expression by immunohistochemistry in 122 formalin-fixed lung tumours including 42 squamous cell carcinoma (SCC), 43 adenocarcinoma (ADC), 19 basaloid carcinoma (BC) and 18 small-cell lung carcinoma (SCLC) in comparison with detection of hTERT l by in situ hybridisation and relative telomerase activity by TRAP assay in a subset of tumours. We observed a high concordance between hTERT protein expression and detection of hTERT mRNA and telomerase activity. Telomerase expression varied according to histology (P = 0.0002) being significantly lower in ADC than in SCC, BC and SCLC (P < 0.0001). Adenocarcinoma and SCC exhibited either a nuclear or a nucleolar staining in contrast with a diffuse nuclear staining observed in most BC and all SCLC (P = 0.01). In stage I NSCLC telomerase expression was lower than in other stages (P = 0.04), and a nucleolar staining was correlated with a short survival (P = 0.03). We concluded that telomerase expression and pattern are distinctive among histopathological classes of lung cancer and convey prognostic influence.
引用
收藏
页码:1222 / 1229
页数:8
相关论文
共 52 条
[31]   TELOMERASE ACTIVITY IN HUMAN BRAIN-TUMORS [J].
LANGFORD, LA ;
PIATYSZEK, MA ;
XU, RS ;
SCHOLD, SC ;
SHAY, JW .
LANCET, 1995, 346 (8985) :1267-1268
[32]   Protein phosphatase 2A inhibits nuclear telomerase activity in human breast cancer cells [J].
Li, H ;
Zhao, LL ;
Funder, JW ;
Liu, JP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (27) :16729-16732
[33]   Cutting edge: Telomerase activation in human T lymphocytes does not require increase in telomerase reverse transcriptase (hTERT) protein but is associated with hTERT phosphorylation and nuclear translocation [J].
Liu, KB ;
Hodes, RJ ;
Weng, NP .
JOURNAL OF IMMUNOLOGY, 2001, 166 (08) :4826-4830
[34]  
Marchetti A, 1999, CLIN CANCER RES, V5, P2077
[35]   Prediction of survival in stage I lung carcinoma patients by telomerase function evaluation [J].
Marchetti, A ;
Pellegrini, C ;
Buttitta, F ;
Falleni, M ;
Romagnoli, S ;
Felicioni, L ;
Barassi, F ;
Salvatore, S ;
Chella, A ;
Angeletti, CA ;
Roncalli, M ;
Coggi, G ;
Bosari, S .
LABORATORY INVESTIGATION, 2002, 82 (06) :729-736
[36]   hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization [J].
Meyerson, M ;
Counter, CM ;
Eaton, EN ;
Ellisen, LW ;
Steiner, P ;
Caddle, SD ;
Ziaugra, L ;
Beijersbergen, RL ;
Davidoff, MJ ;
Liu, QY ;
Bacchetti, S ;
Haber, DA ;
Weinberg, RA .
CELL, 1997, 90 (04) :785-795
[37]   A telomerase component is defective in the human disease dyskeratosis congenita [J].
Mitchell, JR ;
Wood, E ;
Collins, K .
NATURE, 1999, 402 (6761) :551-555
[38]   Reversing time: Origin of telomerase [J].
Nakamura, TM ;
Cech, TR .
CELL, 1998, 92 (05) :587-590
[39]   Telomerase catalytic subunit homologs from fission yeast and human [J].
Nakamura, TM ;
Morin, GB ;
Chapman, KB ;
Weinrich, SL ;
Andrews, WH ;
Lingner, J ;
Harley, CB ;
Cech, TR .
SCIENCE, 1997, 277 (5328) :955-959
[40]   Expression of human telomerase RNA component and telomerase reverse transcriptase mRNA in atypical adenomatous hyperplasia of the lung [J].
Nakanishi, K ;
Kawai, T ;
Kumaki, F ;
Hirot, S ;
Mukai, M ;
Ikeda, E .
HUMAN PATHOLOGY, 2002, 33 (07) :697-702