Katharine L Kirkpatrick1, Robert F Newbold2, Kefah Mokbel3
1Department of Breast Surgery, St George’s Hospital, University of London, United Kingdom
2Institute of Cancer Genetics and Pharmacogenomics, Faculty of Life Sciences, Brunel Universi, United Kingdom
3Department of Breast Surgery, St George’s Hospital, University of London; Institute of Cancer Genetics and Pharmacogenomics, Faculty of Life Sciences, Brunel University, United Kingdom
Background: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) is the rate-limiting determinant of telomerase reactivation. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any correlation between hTERT and the negative prognostic indicators VEGF and PCNA by quantitatively measuring the mRNA expression of these genes in human breast cancer and in adjacent non-cancerous tissue (ANCT).
Materials and methods: RNA was extracted from 38 breast carcinomas and 40 ANCT. hTERT and VEGF165, VEGF189 and PCNA mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology.
Results: The level of expression of VEGF-165 and PCNA was significantly higher in carcinoma tissue than ANCT (p = 0.02). The ratio of VEGF165/189 expression was significantly higher in breast carcinoma than ANCT (p = 0.025). hTERT mRNA expression correlated with VEGF-189 mRNA (p = 0.008) and VEGF165 (p = 0.07).
Conclusions: hTERT mRNA expression is associated with the expression of the VEGF189 and 165 isoforms. This could explain the poorer prognosis reported in breast tumours expressing high levels of hTERT. The relative expression of the VEGF isoforms is significantly different in breast tumour to ANCT, and this may be important in breast carcinogenesis.
Keywords: hTERT, breast, cancer, VEGF, PCNA.