Telomerase and c-myc expression in hepatocellular carcinomas

Abstract

Background. Telomerase is activated in the majority of cancer tissues and immortalized cell lines. The hTERT (human telomerase reverse transcriptase—major component of telomerase) gene promoter has been cloned and contains many c-myc binding sites that mediate hTERT transcriptional activation. Thus far, the role of hTERT in tumorigenesis in hepatocellular carcinoma (HCC) has been little studied using RNA in situ hybridization. The relationship between c-myc and telomerase in human HCC tissue is undetermined. Materials and methods. The telomerase activity was assayed using TRAP in specimens from 23 HCC patients, hTERTmRNA was detected using in situ hybridization from 57 HCC patients. The immunohistochemistry for c-myc and DNA sequence for hTERT promoter, and tumour differentiation in relation to hTERT and c-myc expression were determined in 57 specimens. Result. hTERTmRNA was found in 47/57 (82.5%) HCC specimens using in situ hybridization. The hTERT expression paralleled telomerase activity, but hTERTmRNA regulation was not significantly associated with c-myc level ( P<0.954). The DNA sequence analysis of the hTERT promoter in specimens from 17 HCC revealed 15 cases of nucleotide transition (T→C) over 5′-end of distal E-box and one case of nucleotide transversion (G→C) over 5′-end of proximal E-box. Neither the hTERT expression ( P<0.890) nor c-myc level ( P<0.348) were related to HCC differentiation. Conclusions. The hTERT expression paralleled telomerase activity. The telomerase activity in HCC was not only regulated by c-myc. Another pathways might contribute to hTERT and telomerase activity regulation. The lack of telomerase activity in specimens from 17.4% of HCC cases might indicate an alternative pathway for maintaining telomere length. Furthermore, both the telomerase activity and c-myc had no significant role in HCC differentiation.