[Expression and clinical significance of telomerase catalytic subunit gene in lung cancer and its correlations with genes related to drug resistance and apoptosis].
OBJECTIVE
To investigate mRNA expression and prognostic significance of telomerase catalytic subunit (hTRT/hEST2) and its relations to apoptosis, proliferation and drug resistance in patients with lung cancer.


METHODS
Telomerase repeat amplification protocol-PCR(TRAP-PCR) and in situ hybridization were used to detect telomerase activity and expression of hTRT/hEST2 mRNA, respectively. The expression of bcl-2, c-myc, MRP, Neu, MDR1 at mRNA and protein levels was measured by means of RT-PCR and immunohistochemisty. In situ end labeling(ISEL) assay was used to evaluate apoptotic cells.


RESULTS
hTRT/hEST2 mRNA was detected in 41 of 56 NSCLC(73.2%) and 17 of 20 SCLC(85.0%), but it was not expressed in lung tissues adjacent to the tumor. Telomerase activity was postively correlated with the expression of hTRT/hEST2. In NSCLC, hTRT/hEST2 mRNA was positively correlated with bcl-2(r = 0.7327, P = 0.015), c-myc(r = 0.8263, P = 0.001), MRP(r = 0.3971, P = 0.003) and neu(r = 0.3208, P = 0.017), but not with MDR1 (r = 0.2415, P = 0.672). In SCLC, positive correlation was only found between hTRT/hEST2 and bcl-2 (r = 0.5663, P = 0.024). Correlation was positive between hTRT/hEST2 mRNA and Ki-67 expression but negative between hTRT/hEST2 and apoptosis both in NSCLC and SCLC. Multivariate Cox regression analysis showed that telomerase catalytic subunit hTRT/hEST2 and number of apoptotic cells were of prognostic significance in NSCLC.


CONCLUSIONS
As telomerase catalytic subunit expression shows correlations with MDR- and apoptosis-related genes and is of prognostic significance, telomerase in relation to multiple drug resistance deserves in-depth study.
Wang
J
J
Department of Internal Medicine, School of Oncology, Beijing Medical University, Beijing 100036.
Liu
X
X
Fang
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019098:Telomerase / Q000235:genetics*
D004268:DNA-Binding Proteins; C509186:TERT protein, human; D019098:Telomerase