Normal and Tumour Tissue mRNA Expressions of Telomerase Complex Genes in Several Types of Cancer

Year 2017, Volume: 34 Issue: 3, 269 - 274, 01.05.2017

Emel Çalışkan Can M. Can Atalay Ece Miser Salihoğlu Ülkü Yalçıntaş Arslan H. Bolkan Şimşek Sevgi Yardım Akaydın

Abstract

Aims: To investigate the changes in mRNA expression
levels of telomerase-related significant proteins in
several types of cancer.
Methods: Human telomerase reverse transcriptase,
pontin, reptin and dyskerin expressions were measured
in normal and tumour tissues obtained from 26 patients
with colorectal, breast and gastric cancers, using the realtime
reverse transcriptase-polymerase chain reaction
method.
Results: For all patients, no significant difference was
found in mRNA expressions of human telomerase
reverse transcriptase and dyskerin (p>0.05), although
their levels in tumour tissues were found to be higher
than in normal tissues. However, pontin and reptin
mRNA expressions were significantly higher in
tumour tissues than in normal tissues (p<0.01). While
human telomerase reverse transcriptase showed a high
correlation with only pontin (p<0.001) in normal tissues,
high positive correlations were observed between human
telomerase reverse transcriptase with pontin (p<0.005),
reptin (p<0.01) and dyskerin (p<0.01) in tumour tissues.
Conclusion: The increased mRNA expressions of all
four genes in tumour tissues may suggest a role in cancer
development. Correlations of pontin, reptin and dyskerin
with human telomerase reverse transcriptase support
the hypotheses describing their roles in telomerase
complexes

Keywords

Human telomerase reverse transcriptase, pontin, reptin, dyskerin, telomerase, cancer

References

• 1. Venteicher AS, Meng Z, Mason PJ, Veenstra TD, Artandi SE. Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly. Cell 2008;132:945-57.
• 2. Baek SH. When ATPases pontin and reptin met telomerase. Dev Cell 2008;459-61.
• 3. Wang Z, Xu J, Geng X, Zhang W. Analysis of DNA methylation status of the promoter of human telomerase reverse transcriptase in gastric carcinogenesis. Arch Med Res 2010;41:1-6.
• 4. Shay JW, Wright WE. Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov 2006;5:577-84.
• 5. Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 1999;402:551-5.
• 6. Montanaro L, Calienni M, Ceccarelli C, Santini D, Taffurelli M, Pileri S, et al. Relationship between dyskerin expression and telomerase activity in human breast cancer. Cell Oncol 2008;30:483-90.
• 7. Neuwald AF, Aravind L, Spouge JL, Koonin EV. AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res 1999;927-43.
• 8. Kim T, Franke D, Svergun DI, Kim KK. SAXS analyses of reption in solution. [Internet]. 2007. [cited 2009 Jun 29]. Available from: http://hasyweb.desy. de/science/annual_reports/2007_report/part2/contrib/73/20982.pdf
• 9. Jha S, Dutta A. RVB1/RVB2: running rings around molecular biology. Mol Cell 2009;34:521-33.
• 10. Greene FL, Compton CC, Fritz AG, Shah JP, Winchester DP. AJCC cancer staging atlas, Springer Science+Business Media Inc, Chicago: USA; 2006. 11. Dikmen G, Doğan P. Telomeraz ve kanser. Turk Klin Tip Bilim 2003;23:334-41.
• 12. Flavin P, Redmond A, McBryan J, Cocchiglia S, Tibbitts P, Fahy-Browne P, et al. RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer. FEBS Lett 2011;585:2537-44.
• 13. Ahmed A, Tollefsbol TO. Telomerase, telomerase inhibition, and cancer. J Anti Aging Med 2003;6:315-25.
• 14. Cairney CJ, Keith WN. Telomerase redefined: Integrated regulation of hTR and hTERT for telomere maintenance and telomerase activity. Biochimie 2008;90:13-23.
• 15. Palmqvist R, Zhang A, Xu D, Golovleva I, Norrback KF, Gruber A, et al. hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer. Int J Cancer 2005;116:395- 400.
• 16. Saleh S, Lam AK, Ho YH. Real-time PCR quantification of human telomerase reverse transcriptase (hTERT) in colorectal cancer. Pathology 2008;40:25-30.
• 17. Elkak A, Mokbel R, Wilson C, Jiang WG, Newbold RF, Mokbel K. hTERT mRNA expression is associated with a poor clinical outcome in human breast cancer. Anticancer Res 2006;26:4901-4.
• 18. Montanaro L, Brigotti M, Clohessy J, Barbieri S, Ceccarelli C, Santini D, et al. Dyskerin expression influences the level of ribosomal RNA pseudouridylation and telomerase RNA component in human breast cancer. J Pathol 2006;210:10-8.
• 19. Huber O, Ménard L, Haurie V, Nicou A, Taras D, Rosenbaum J. Pontin and reptin, two related ATPases with multiple roles in cancer. Cancer Res 2008;68:6873-6.
• 20. Li W, Zeng J, Li Q, Zhao L, Liu T, Björkholm M, et al. Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer. Mol Cancer 2010;9:132.