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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.

Khosravi-Maharlooei M, Jaberipour M, Hosseini Tashnizi A, Attar A, Amirmoezi F, Habibagahi M - Int J Mol Cell Med (2015)

Bottom Line: 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.In spite that, the regulatory roles of hTERT on telomerase activity is still a potential to be utilized as targets for cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: Student Research Committee, Cell and Molecular Medicine Research Group, 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.

No MeSH data available.


Related in: MedlinePlus

Correlation between the expression of full length hTERT variants and other alternative forms . The Spearman’s correlation coefficient was used to find statistical relation between the expression of full length hTERT transcript and the three spliced variants. The expression of full length transcript in the cells with telomerase activity was found in significant association with both β-variant (■ symbol, sold line, P= 0.0007, r= 0.74) and then α-variant (● symbol, broken line, P= 0.001, r= 0.7) but not α/β-deleted variant (▲ symbol, dotted line, P= 0.002, r= 0.68). There was no statistically significant correlation between the expression of the full length variant and other variants in the telomerase negative cells (P< 0.3, r< 0.3).
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Figure 5: Correlation between the expression of full length hTERT variants and other alternative forms . The Spearman’s correlation coefficient was used to find statistical relation between the expression of full length hTERT transcript and the three spliced variants. The expression of full length transcript in the cells with telomerase activity was found in significant association with both β-variant (■ symbol, sold line, P= 0.0007, r= 0.74) and then α-variant (● symbol, broken line, P= 0.001, r= 0.7) but not α/β-deleted variant (▲ symbol, dotted line, P= 0.002, r= 0.68). There was no statistically significant correlation between the expression of the full length variant and other variants in the telomerase negative cells (P< 0.3, r< 0.3).

Mentions: As it was shown in Figure 3 the full length hTERT variant was the most common variant expressed in the studied cell lines. Spearman’s correlation analysis showed that the expression of this variant in the cells with telomerase activity was in significant association with both β-variant (P= 0.0007, r = 0.74) and then α-variant (P= 0.001, r= 0.7). The expression of full length hTERT was in a weak correlation with α/β-deleted variant (P= 0.002, r= 0.68) (Figure 5). Similar study in the cells with no detectable telomerase activity could not show significant correlation between the expression of the full length variant (P<0.3, r<0.3). However, α-deleted variant had greater expression in telomerase negative cells (P= 0.04). No statistically meaningful correlation was found between telomerase activity and proliferation capacity (doubling time) of the cell lines (P=0.92, r= 0.0001). Similarly, no significant correlation between the expression of hTERT variants and telomerase activity or doubling time of the studied cancer cell lines was discovered.


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.

Khosravi-Maharlooei M, Jaberipour M, Hosseini Tashnizi A, Attar A, Amirmoezi F, Habibagahi M - Int J Mol Cell Med (2015)

Correlation between the expression of full length hTERT variants and other alternative forms . The Spearman’s correlation coefficient was used to find statistical relation between the expression of full length hTERT transcript and the three spliced variants. The expression of full length transcript in the cells with telomerase activity was found in significant association with both β-variant (■ symbol, sold line, P= 0.0007, r= 0.74) and then α-variant (● symbol, broken line, P= 0.001, r= 0.7) but not α/β-deleted variant (▲ symbol, dotted line, P= 0.002, r= 0.68). There was no statistically significant correlation between the expression of the full length variant and other variants in the telomerase negative cells (P< 0.3, r< 0.3).
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Figure 5: Correlation between the expression of full length hTERT variants and other alternative forms . The Spearman’s correlation coefficient was used to find statistical relation between the expression of full length hTERT transcript and the three spliced variants. The expression of full length transcript in the cells with telomerase activity was found in significant association with both β-variant (■ symbol, sold line, P= 0.0007, r= 0.74) and then α-variant (● symbol, broken line, P= 0.001, r= 0.7) but not α/β-deleted variant (▲ symbol, dotted line, P= 0.002, r= 0.68). There was no statistically significant correlation between the expression of the full length variant and other variants in the telomerase negative cells (P< 0.3, r< 0.3).
Mentions: As it was shown in Figure 3 the full length hTERT variant was the most common variant expressed in the studied cell lines. Spearman’s correlation analysis showed that the expression of this variant in the cells with telomerase activity was in significant association with both β-variant (P= 0.0007, r = 0.74) and then α-variant (P= 0.001, r= 0.7). The expression of full length hTERT was in a weak correlation with α/β-deleted variant (P= 0.002, r= 0.68) (Figure 5). Similar study in the cells with no detectable telomerase activity could not show significant correlation between the expression of the full length variant (P<0.3, r<0.3). However, α-deleted variant had greater expression in telomerase negative cells (P= 0.04). No statistically meaningful correlation was found between telomerase activity and proliferation capacity (doubling time) of the cell lines (P=0.92, r= 0.0001). Similarly, no significant correlation between the expression of hTERT variants and telomerase activity or doubling time of the studied cancer cell lines was discovered.

Bottom Line: 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.In spite that, the regulatory roles of hTERT on telomerase activity is still a potential to be utilized as targets for cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: Student Research Committee, Cell and Molecular Medicine Research Group, 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.

No MeSH data available.


Related in: MedlinePlus