Abstract
Human telomerase is expressed in germ tissues and in the majority of primary tumors. Cell renewal tissues and some pre-cancerous tissues also have weak telomerase activity. Yet, neither the exact location and frequency of telomerase-positive cells nor the changes in telomerase expression during differentiation or carcinogenesis of individual cells are known. This paper reports on the expression of hTERT (telomerase reverse transcriptase) protein in tumor and non-tumor colorectal tissues by Western blotting and tissue sections by immuno-histochemistry using antibodies raised against partial peptides of hTERT. Though telomerase activity and hTERT expression at both mRNA and protein levels were generally higher in tumor part than in non-tumor part, these two were not always correlated: expression of hTERT did not always give rise to high telomerase activity. Colonic carcinoma cell nuclei were stained with anti-hTERT antibodies but not with antigen-preabsorbed antibodies. In normal mucosa, hTERT protein was expressed, though weaker than in carcinoma, in all colonic crypt epithelial cells except those at the tip; the expressing-cell distribution was much wider than that of Ki-67 positive cells which were located at the bottom of the crypt. Isolated crypt contained a significant level of hTERT protein revealed by Western blotting, while having very weak telomerase activity. Telomerase activity was detected in epithelial cells only at the bottom half of the crypt. Specific hTERT-staining was positive in tissue lymphocytes but negative in almost all other stromal cells. It is of interest to see whether a significant level of hTERT expression with low telomerase activity is characteristic of physiologically regenerating tissues containing stem cells. In situ detection of the hTERT protein will permit further analysis of cancer diagnosis and stem cell differentiation.
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Abbreviations
- RT – PCR:
-
reverse transcribed-polymerase chain reaction
- TRAP:
-
telomeric repeat amplification protocol
- hTERT:
-
human telomerase reverse transcriptase
- hTERC:
-
human telomerase RNA component
- hTEP1:
-
human telomerase protein 1
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Acknowledgements
We thank Drs K Inada and M Tatematsu (Aichi Cancer Center Institute) for technical suggestions of crypt isolation and Dr J Carl Barrett (National Institute of Environmental Health Sciences, NIH) for critical reading of and useful comments on this manuscript. This work was supported in part by Grant-in-Aid for Cancer Research and a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, and Culture of Japan.
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Tahara, H., Yasui, W., Tahara, E. et al. Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections. Oncogene 18, 1561–1567 (1999). https://doi.org/10.1038/sj.onc.1202458
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DOI: https://doi.org/10.1038/sj.onc.1202458
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