[Telomerase, cell immortality and cancer].

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Telomerase maintains chromosome ends, crucial for cellular immortality and implicated in carcinogenesis.
• Telomerase activity is typically repressed in normal somatic tissues but activated in over 85% of malignant tumors.
• Gastric mucosal tissues exhibit varying telomerase activity, with higher levels in cancer, intestinal metaplasia, and chronic gastritis.

Purpose of the Study:

• To investigate telomerase activity in gastric mucosal tissues and its correlation with H. pylori infection.
• To establish quantitative assays for key telomerase components (hTR, hTERT, TEP1) and telomeric repeat binding factors (TRF1, TRF2).
• To elucidate the regulatory roles of hTERT, TRF1, and TRF2 in telomerase activity.

Main Methods:

• Quantitative TaqMan RT-PCR assays were developed to measure mRNA levels of hTR, hTERT, TEP1, TRF1, and TRF2.
• Telomerase activity was assessed in gastric cancer, intestinal metaplasia, chronic gastritis, and normal mucosa.
• Gene expression analysis was performed in normal cells, malignant hematopoietic cell lines, and during HL60 cell differentiation.

Main Results:

• Telomerase activity was highest in gastric cancer, followed by intestinal metaplasia, chronic gastritis, and normal mucosa.
• H. pylori infection was associated with higher telomerase activity in intestinal metaplasia and intestinal-type gastric cancer.
• Expression of TRF1 and TRF2 mRNA was higher in normal cells than in malignant cells, and their expression increased during HL60 cell differentiation, while hTERT expression paralleled telomerase activity.

Conclusions:

• Telomerase activity is a significant marker in gastric tissue progression and is influenced by H. pylori infection.
• hTERT, TRF1, and TRF2 are identified as crucial regulators of telomerase activity.
• Quantitative assays for telomerase components provide valuable tools for further research in cancer gene therapy targets.