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Published in: Cancer Cell International 1/2003

Open Access 01-12-2003 | Primary research

Is telomerase reactivation associated with the down-regulation of TGF β receptor-II expression in human breast cancer?

Authors: Abd E Elkak, Robert F Newbold, Valene Thomas, Kefah Mokbel

Published in: Cancer Cell International | Issue 1/2003

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Abstract

Background

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.
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Literature
1.
go back to reference Morin GB: The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesises TTAGGG repeats. Cell. 1989, 59: 521-9.CrossRefPubMed Morin GB: The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesises TTAGGG repeats. Cell. 1989, 59: 521-9.CrossRefPubMed
2.
go back to reference Counter CM, Avilion AA, LeFeuvre CE: Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 1992, 11: 1921-1929.PubMedCentralPubMed Counter CM, Avilion AA, LeFeuvre CE: Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 1992, 11: 1921-1929.PubMedCentralPubMed
3.
4.
go back to reference Kim NW, Piatyszek MA, Prowse KR: Specific association of human telomerase activity with immortal cells and cancer. Science. 1994, 266: 2011-15.CrossRefPubMed Kim NW, Piatyszek MA, Prowse KR: Specific association of human telomerase activity with immortal cells and cancer. Science. 1994, 266: 2011-15.CrossRefPubMed
5.
go back to reference Rhyu MS: Telomeres, Telomeres and immortality. J Natl Cancer Inst. 1995, 87: 884-94. 10.1093/jnci/87.12.884.CrossRefPubMed Rhyu MS: Telomeres, Telomeres and immortality. J Natl Cancer Inst. 1995, 87: 884-94. 10.1093/jnci/87.12.884.CrossRefPubMed
6.
go back to reference Mokbel K, Ghilchik M, Williams G: The association between telomerase activity and hormone receptor status and p53 expression in breast cancer. Int J Surg Investig. 2000, 1: 509-16.PubMed Mokbel K, Ghilchik M, Williams G: The association between telomerase activity and hormone receptor status and p53 expression in breast cancer. Int J Surg Investig. 2000, 1: 509-16.PubMed
7.
go back to reference Mokbel K, Parris CN, Ghilchik M: The association between telomerase activity, histopathological parameters and Ki-67 expression in invasive breast cancer. Am J Surg. 1999, 178: 69-72. 10.1016/S0002-9610(99)00128-2.CrossRefPubMed Mokbel K, Parris CN, Ghilchik M: The association between telomerase activity, histopathological parameters and Ki-67 expression in invasive breast cancer. Am J Surg. 1999, 178: 69-72. 10.1016/S0002-9610(99)00128-2.CrossRefPubMed
8.
go back to reference Mokbel K, Parris CN, Ghilchik M: Telomerase activity and lymphovascular invasion in breast cancer. Eur J Surg Oncol. 2000, 26: 30-3. 10.1053/ejso.1999.0736.CrossRefPubMed Mokbel K, Parris CN, Ghilchik M: Telomerase activity and lymphovascular invasion in breast cancer. Eur J Surg Oncol. 2000, 26: 30-3. 10.1053/ejso.1999.0736.CrossRefPubMed
9.
go back to reference Blobe GC, Schiemann WP, Lodish HF: Role of transforming growth factor beta in human disease. N Engl J Med. 2000, 342: 1350-8. 10.1056/NEJM200005043421807.CrossRefPubMed Blobe GC, Schiemann WP, Lodish HF: Role of transforming growth factor beta in human disease. N Engl J Med. 2000, 342: 1350-8. 10.1056/NEJM200005043421807.CrossRefPubMed
10.
go back to reference Clark DA, Coker R: Transforming growth factor beta (TGF beta). Int J Biochem Cell Biol. 1998, 30: 293-8. 10.1016/S1357-2725(97)00128-3.CrossRefPubMed Clark DA, Coker R: Transforming growth factor beta (TGF beta). Int J Biochem Cell Biol. 1998, 30: 293-8. 10.1016/S1357-2725(97)00128-3.CrossRefPubMed
11.
go back to reference Miyazono K: Positive and negative regulation of TGF beta signalling. J Cell Sci. 2000, 113: 1101-9.PubMed Miyazono K: Positive and negative regulation of TGF beta signalling. J Cell Sci. 2000, 113: 1101-9.PubMed
12.
go back to reference Wang X-F, Lin HY, Ng-Eaton E: Expression cloning and characterization of the TGF beta type III receptor. Cell. 1991, 67: 797-805.CrossRefPubMed Wang X-F, Lin HY, Ng-Eaton E: Expression cloning and characterization of the TGF beta type III receptor. Cell. 1991, 67: 797-805.CrossRefPubMed
13.
go back to reference Massague J: TGF beta signal transduction. Ann Rev Biochem. 1998, 67: 753-791. 10.1146/annurev.biochem.67.1.753.CrossRefPubMed Massague J: TGF beta signal transduction. Ann Rev Biochem. 1998, 67: 753-791. 10.1146/annurev.biochem.67.1.753.CrossRefPubMed
14.
go back to reference Lin HY, Wang X-F, Ng-Eaton E: Expression cloning of the TGF beta type II receptor, a functional transmembrane serine/ threonine kinase. Cell. 1992, 68: 775-785.CrossRefPubMed Lin HY, Wang X-F, Ng-Eaton E: Expression cloning of the TGF beta type II receptor, a functional transmembrane serine/ threonine kinase. Cell. 1992, 68: 775-785.CrossRefPubMed
15.
go back to reference Huse M, Chen Y-G, Massague J: Crystal Structure of the cytoplasmic domain of type I TGF beta receptor in complex with FKBP 12. Cell. 1999, 96: 425-436.CrossRefPubMed Huse M, Chen Y-G, Massague J: Crystal Structure of the cytoplasmic domain of type I TGF beta receptor in complex with FKBP 12. Cell. 1999, 96: 425-436.CrossRefPubMed
16.
go back to reference Wrana JL, Attisano L, Carcamo J: TGF beta signals through a heteromeic protein kinase receptor complex. Cell. 1992, 71: 1003-1014.CrossRefPubMed Wrana JL, Attisano L, Carcamo J: TGF beta signals through a heteromeic protein kinase receptor complex. Cell. 1992, 71: 1003-1014.CrossRefPubMed
17.
go back to reference Grady WM, Myeroff LL, Swinler SE: Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers. Cancer Res. 1999, 59: 320-4.PubMed Grady WM, Myeroff LL, Swinler SE: Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers. Cancer Res. 1999, 59: 320-4.PubMed
18.
go back to reference Hojo M, Morimoto T, Maluccio M: Cyclosporine induces cancer progression by a cell autonomous mechanism. Nature. 1999, 397: 530-4. 10.1038/17401.CrossRefPubMed Hojo M, Morimoto T, Maluccio M: Cyclosporine induces cancer progression by a cell autonomous mechanism. Nature. 1999, 397: 530-4. 10.1038/17401.CrossRefPubMed
19.
go back to reference Yang H, Kyo S, Takatura M: Autocrine transforming growth factor beta suppresses telomerase activity and transcription of human telomerase reverse transcriptase in human cancer cells. Cell Growth Differ. 2001, 12: 119-27.PubMed Yang H, Kyo S, Takatura M: Autocrine transforming growth factor beta suppresses telomerase activity and transcription of human telomerase reverse transcriptase in human cancer cells. Cell Growth Differ. 2001, 12: 119-27.PubMed
20.
go back to reference Gobbi H, Arteaga CL, Jensen RA: Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in-situ and invasive carcinomas. Histopathology. 2000, 36: 168-77. 10.1046/j.1365-2559.2000.00841.x.CrossRefPubMed Gobbi H, Arteaga CL, Jensen RA: Loss of expression of transforming growth factor beta type II receptor correlates with high tumour grade in human breast in-situ and invasive carcinomas. Histopathology. 2000, 36: 168-77. 10.1046/j.1365-2559.2000.00841.x.CrossRefPubMed
21.
go back to reference Kirkpatrick KL, Clarke G, Ghilchik M, Newbold RF, Mokbel K: Telomerase activity correlates with hTERT mRNA expression in human breast cancer. Eur J Surg Oncol. 2002, Kirkpatrick KL, Clarke G, Ghilchik M, Newbold RF, Mokbel K: Telomerase activity correlates with hTERT mRNA expression in human breast cancer. Eur J Surg Oncol. 2002,
Metadata
Title
Is telomerase reactivation associated with the down-regulation of TGF β receptor-II expression in human breast cancer?
Authors
Abd E Elkak
Robert F Newbold
Valene Thomas
Kefah Mokbel
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2003
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-3-9

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