The Expression Of Human Telomerase Reverse Transcriptase In Non-small-cell Lung Cancer And Its Relationship With Multi-drug Resistance

Objective : To detect the expressions of human telomerase reverse transcriptase mRNA (hTERT mRNA), c-myc, protein kinase Ca(PKCa) as well as mutant P53 in non-small-cell lung carcinoma (NSCLC) , analyze the relationship of the four markers with clinic-pathological factors and correlation among the four markers, and elucidate the regulatory mechanism of high expression level of hTERT mRNA in NSCLC; To investigate expressions and clinic-pathological significance of multidrug resistance (MDR) gene or proteins including MDR 1 mRNA , multidrug resistance associated protein( MRP) and lung resistance associated protein( LRP) in NSCLC, analyze the relationship between hTERT mRNA and MDR, and elucidate the mechanisms of multi-drug resistance existed in NSCLC.Methods: 113 specimens of NSCLC were all from Department of Pathology of Wuhan University Zhongnan Hospital, which included 39 samples of squamous cell carcinoma, 61 samples of adenocarcinoma and 13 samples of adeno-squamous carcinoma. The expressions of hTERT mRNA and MDRlmRNA were detected by in situ hybridization(ISH) method , and the expressions of c-myc, mutant P53 , PKCa, MRP and LRP were detected by strepavidin-peroxidase(SP)immunohistochemistry method.Results: (1) The positive rates of 113 NSCLC samples for hTERT mRNA, c-myc, PKCa, mutant P53 were 80.5%, 68.1%, 85.0%, 61.9% respectively. No correlation was observed among the expressions of hTERT mRNA, c-myc and PKCa with clinic-pathological factors(P>0.05). The expression of mutant p53 was associated with carcinoma cell differentiation (P<0.05), its positive rate gradually increased from well differentiation to poor differentiation of carcinoma cell. (2)Correlation were statistically significant among the expressions of hTERT mRNA , c-myc and PKCa(P<0.05 or P< 0.01). (3)The positive rates of 113 NSCLC samples for MRP, MDRlmRNA and LRP were 79.6%, 51.3% and 80.5% respectively. Significant correlation was observed among the expressions of MRP, LRP with histological types(P <0.05), but not observed between theexpression of MDRlmRNA and histological types (P>0.05). There are no relation among the expressions of three MDR markers and differentiation degree, TNM, lymph node metastasis states of NSCLC (P>0.05).(4)The expression of MRP was related with LRP (P <0.01) but not with MDRlmRNA(P>.05). (5)The expression of hTERT mRNA was related with MRP, MDRlmRNA (P<0.01; P<0.05).Conclusions : (1)In NSCLC, correlation among hTERT mRNA, c-myc and PKCa suggested c-myc and PKCa could be positive regulators of human telomerase reverse transcriptase , and c-myc could cooperate with PKCa to foster reactivation of telomerase in non-small cell lung carcinoma. (2)Mutant p53 gene could be related with differentiation degree of NSCLC. (3)Different histological types of NSCLC had different expression of multi-drug resistance related genes or protiens. There were some relationship between the expressions of MRP , LRP and histological types , but not between the expression of MDRlmRNA and histological types. And positive relation between MRP and LRP existed in NSCLC. (4)Correlation between hTERT mRNA and MDRlmRNA, MRP suggested that activated telomerase could be a new mechanism of multi-drug resistance existed in NSCLC.