[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.

CONCLUSION

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.