Elkak Abd E, Newbold Robert F, Thomas Valene, Mokbel Kefah
St George's Hospital and Medical School, London, UK.
Cancer Cell Int. 2003 Jul 6;3(1):9. doi: 10.1186/1475-2867-3-9.
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. 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. METHODS: TGF 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. RESULTS: TGF 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). CONCLUSION: The 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.
端粒酶是一种核糖核蛋白,可合成端粒,在染色体稳定性和细胞永生化中起重要作用。端粒酶活性在大多数人类癌症中可检测到,但在正常体细胞中则不然。转化生长因子β(TGFβ)是细胞因子家族的成员,对细胞存活至关重要,且在人类癌症中似乎下调。最近使用人乳腺癌细胞系的体外研究表明,TGFβ下调端粒酶催化亚基人端粒酶逆转录酶(hTERT)的表达。因此,我们推测端粒酶重新激活与人乳腺癌中II型TGFβ受体(RII)免疫组化表达降低有关。
在24例已知端粒酶活性的浸润性乳腺癌(17例端粒酶阳性和7例端粒酶阴性)中测定TGFβRII免疫组化表达。TGFβRII的免疫组化表达由一位对端粒酶数据不知情的乳腺病理学家确定。
在所有病变中均检测到TGFβRII。染色细胞的百分比范围为1%-100%。端粒酶阳性和阴性肿瘤之间TGFβRII表达的差异无统计学意义(p = 1.0)。
这项初步研究的结果表明,在人类乳腺癌中端粒酶重新激活与TGF-βRII下调之间没有显著关联。