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.
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.
Student Research Committee, Cell and Molecular Medicine Research Group, Shiraz University of Medical Sciences, Shiraz, Iran.
Mohsen
M
Khosravi-Maharlooei
Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.
Mansooreh
M
Jaberipour
Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.
Ahmad
A
Hosseini Tashnizi
Student Research Committee, Cell and Molecular Medicine Research Group, Shiraz University of Medical Sciences, Shiraz, Iran.
Armin
A
Attar
Student Research Committee, Cell and Molecular Medicine Research Group, Shiraz University of Medical Sciences, Shiraz, Iran.
Fatemeh
F
Amirmoezi
Immunotherapy Laboratory, Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Mojtaba
M
Habibagahi
Alternative splicing; cancer cell line; hTERT variants; proliferation capacity; telomerase activity