Expression Pattern of Alternative Splicing Variants of Human Telomerase Reverse Transcriptase (hTERT) in Cancer Cell Lines Was not Associated with the Origin of the Cells

Document Type : Original Article

Authors
Mohsen Khosravi- Maharlooei 1
Mansooreh Jaberipour 2
Ahmad Hosseini Tashnizi 2
Armin Attar 1
Fatemeh Amirmoezi 1
Mojtaba Habibagahi 3
1 Student Research Committee, Cell and Molecular Medicine Research Group, Shiraz University of Medical Sciences, Shiraz, Iran
2 Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran
3 Immunotherapy Laboratory, Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
Telomerase and systems controlling their activity have been of great attention. There are controversies regarding
the role of the alternative splicing forms of the human telomerase reverse transcriptase (hTERT), the catalytic
subunit of telomerase. Therefore, the correlation between telomerase enzyme activity, the abundance of
alternatively spliced variants of hTERT and doubling time of a series of cancer cell lines originated from
hematopoietic, breast, colorectal, neural, ovarian, lung, kidney, bladder, prostate and head and neck cancers were investigated. Expression levels of four different variants of hTERT (the full length, α-deletion, β-deletion and α/β-deletion) were quantitatively measured by real time PCR. Telomerase activity was determined by the
telomerase repeat amplification protocol (TRAP) while doubling time of the cells measured by plotting growth
curves. Results showed high diversity in the relative proportions of hTERT transcripts while the majority of the
cells expressed the full length variant as the main transcript. Telomerase activity could not be detected in all cells. Relative assessment of hTERT expression showed greater expression of the α-deleted variant in the telomerase negative cells (P= 0.04). Those cells possessed the α/β-deleted variant to a smaller extent when compared to the cells with telomerase activity. Greater association between full length spliced variant and β-
variant expression was observed in cells presenting telomerase activity (P= 0.0007, r= 0.74). High degrees of
variation among the studied cells regarding the pattern of hTERT expression were present. In spite that, the
regulatory roles of hTERT on telomerase activity is still a potential to be utilized as targets for cancer therapies.
Keywords
Alternative splicing
cancer cell line
hTERT variants
proliferation capacity
telomerase activity