Telomerase in (pre)neoplastic cervical disease.

Area of Science:

• Oncology
• Molecular Biology
• Gynecology

Background:

• Telomerase is crucial for cellular immortalization and is often dysregulated in cancer.
• The human telomerase RNA component (hTR) and catalytic subunit mRNA (hTERT) are key components of telomerase.
• Cervical (pre)malignant lesions, such as cervical intraepithelial neoplasia (CIN), are associated with human papillomavirus (HPV) infection.

Purpose of the Study:

• To investigate the upregulation of hTR and hTERT mRNA in cervical lesions.
• To analyze intralesional heterogeneity of hTR expression.
• To correlate hTR and hTERT mRNA levels with telomerase activity and HPV status.

Main Methods:

• In situ hybridization (ISH) for hTR expression on paraffin-embedded cervical tissues (CIN I-III, cervical cancer, normal controls).
• Quantitative reverse transcription polymerase chain reaction (rt-PCR) for hTR and hTERT mRNA on frozen cervical lesion samples.
• Analysis of existing data on telomerase activity and HPV typing.

Main Results:

• hTR expression by ISH was significantly more frequent in higher grades of CIN and cervical cancer compared to normal cervices (P<.001).
• hTERT mRNA expression by rt-PCR also correlated with the grade of CIN/cervical cancer (P<.01).
• Both hTR (ISH) and hTERT mRNA (rt-PCR) levels were associated with increased telomerase activity and the presence of oncogenic HPV types (P<.05).

Conclusions:

• Frequent upregulation of hTR and hTERT mRNA occurs in cervical (pre)malignant lesions.
• This upregulation appears to precede the induction of significant telomerase activity.
• The coordinated upregulation of both telomerase components is likely important for functional telomerase in cervical carcinogenesis.