Abstract
BackgroundTelomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation. Telomerase activity is detectable in most human cancers but not in normal somatic cells. TGF beta (transforming growth factor beta) is a member of a family of cytokines that are essential for cell survival and seems to be down-regulated in human cancer. Recent in vitro work using human breast cancer cell lines has suggested that TGF beta down-regulates the expression of hTERT (human telomerase reverse transcriptase) : the catalytic subunit of telomerase. We have therefore hypothesised that telomerase reactivation is associated with reduced immunohisto-chemical expression of TGF beta type II receptor (RII) in human breast cancer.MethodsTGF beta RII immunohistochemical expression was determined in 24 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 7 telomerase-negative). Immunohistochemical expression of TGF beta RII was determined by a breast pathologist who was blinded to telomerase data.ResultsTGF beta RII was detected in all lesions. The percentage of stained cells ranged from 1–100%. The difference in TGF beta RII expression between telomerase positive and negative tumours was not statistically significant (p = 1.0).ConclusionThe results of this pilot study suggest that there is no significant association between telomerase reactivation and TGF-beta RII down-regulation in human breast cancer.
Highlights
Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation
The present study aims to examine the relationship between telomerase and TGF beta RII in human breast cancer
This pilot study shows no significant association between telomerase reactivation and TGF beta RII expression in human breast cancer specimens
Summary
Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation. Telomerase activity is detectable in most human cancers but not in normal somatic cells. Recent in vitro work using human breast cancer cell lines has suggested that TGF beta down-regulates the expression of hTERT (human telomerase reverse transcriptase) : the catalytic subunit of telomerase. We have hypothesised that telomerase reactivation is associated with reduced immunohisto-chemical expression of TGF beta type II receptor (RII) in human breast cancer. Cancer Cell International 2003, 3 http://www.cancerci.com/content/3/1/9 expressing the enzyme telomerase which contains an RNA complementary to telomeric AGGGTT repeats that permits telomere synthesis onto chromosomal ends [4]. Using a polymerase chain reaction (PCR)-based assay called the TRAP (telomeric repeat and amplification protocol) assay telomerase activity has been detected in most malignant and germline cells but not in normal somatic cells[4]. We previously reported telomerase activity in 72% of human breast carcinomas and in none of normal or benign breast tissue specimens [6] we observed a significant association between telomerase activity and recognised prognostic indicators such as nodal status, tumour size, Ki-67 expression and lymphovascular invasion [7,8]
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