Depletion of signal recognition particle 72kDa increases radiosensitivity

The identification of genetic determinants that underpin tumor radioresistance can help the development of targeted radiosensitizers or aid personalization of radiotherapy treatment. Here we identify signal recognition particle 72kDa (SRP72) as a novel gene involved in radioresistance. Knockdown of...

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Vydáno v:Cancer biology & therapy Ročník 18; číslo 6; s. 425 - 432
Hlavní autoři: Prevo, Remko, Tiwana, Gaganpreet S., Maughan, Timothy S., Buffa, Francesca M., McKenna, W. Gillies, Higgins, Geoff S.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Taylor & Francis 03.06.2017
Témata:
Apoptosis
Cell Survival - radiation effects
clonogenic assay
Gene Knockdown Techniques
HeLa Cells
Humans
MCF-7 Cells
Protein Biosynthesis
Radiation Tolerance
radiosensitivity
radiotherapy
Research Paper
signal recognition particle
Signal Recognition Particle - genetics
Signal Recognition Particle - metabolism
siRNA
SRP72
Unfolded Protein Response
signal recognition particle
unfolded protein response
SRP72
clonogenic assay
radiosensitivity
radiotherapy
siRNA
Apoptosis
ISSN:1538-4047, 1555-8576, 1555-8576
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Abstract The identification of genetic determinants that underpin tumor radioresistance can help the development of targeted radiosensitizers or aid personalization of radiotherapy treatment. Here we identify signal recognition particle 72kDa (SRP72) as a novel gene involved in radioresistance. Knockdown of SRP72 resulted in significant radiosensitization of HeLa (cervical), PSN-1 (pancreatic), and T24 (bladder), BT-549 (breast) and MCF7 (breast) tumor lines as measured by colony formation assays. SRP72 depletion also resulted in the radiosensitization of normal lung fibroblast cell lines (HFL1 and MRC-5), demonstrating that the effect is not restricted to tumor cells. Increased radiosensitivity was not due to impaired DNA damage signaling or repair as assessed by γ-H2AX foci formation. Instead SRP72 depletion was associated with elevated levels of apoptosis after irradiation, as measured by caspase 3/7 activity, PARP-cleavage and Annexin-V staining, and with an induction of the unfolded protein response. Together, our results show that SRP72 is a novel gene involved in radioresistance.
AbstractList The identification of genetic determinants that underpin tumor radioresistance can help the development of targeted radiosensitizers or aid personalization of radiotherapy treatment. Here we identify signal recognition particle 72kDa (SRP72) as a novel gene involved in radioresistance. Knockdown of SRP72 resulted in significant radiosensitization of HeLa (cervical), PSN-1 (pancreatic), and T24 (bladder), BT-549 (breast) and MCF7 (breast) tumor lines as measured by colony formation assays. SRP72 depletion also resulted in the radiosensitization of normal lung fibroblast cell lines (HFL1 and MRC-5), demonstrating that the effect is not restricted to tumor cells. Increased radiosensitivity was not due to impaired DNA damage signaling or repair as assessed by γ-H2AX foci formation. Instead SRP72 depletion was associated with elevated levels of apoptosis after irradiation, as measured by caspase 3/7 activity, PARP-cleavage and Annexin-V staining, and with an induction of the unfolded protein response. Together, our results show that SRP72 is a novel gene involved in radioresistance.The identification of genetic determinants that underpin tumor radioresistance can help the development of targeted radiosensitizers or aid personalization of radiotherapy treatment. Here we identify signal recognition particle 72kDa (SRP72) as a novel gene involved in radioresistance. Knockdown of SRP72 resulted in significant radiosensitization of HeLa (cervical), PSN-1 (pancreatic), and T24 (bladder), BT-549 (breast) and MCF7 (breast) tumor lines as measured by colony formation assays. SRP72 depletion also resulted in the radiosensitization of normal lung fibroblast cell lines (HFL1 and MRC-5), demonstrating that the effect is not restricted to tumor cells. Increased radiosensitivity was not due to impaired DNA damage signaling or repair as assessed by γ-H2AX foci formation. Instead SRP72 depletion was associated with elevated levels of apoptosis after irradiation, as measured by caspase 3/7 activity, PARP-cleavage and Annexin-V staining, and with an induction of the unfolded protein response. Together, our results show that SRP72 is a novel gene involved in radioresistance.
The identification of genetic determinants that underpin tumor radioresistance can help the development of targeted radiosensitizers or aid personalization of radiotherapy treatment. Here we identify signal recognition particle 72kDa (SRP72) as a novel gene involved in radioresistance. Knockdown of SRP72 resulted in significant radiosensitization of HeLa (cervical), PSN-1 (pancreatic), and T24 (bladder), BT-549 (breast) and MCF7 (breast) tumor lines as measured by colony formation assays. SRP72 depletion also resulted in the radiosensitization of normal lung fibroblast cell lines (HFL1 and MRC-5), demonstrating that the effect is not restricted to tumor cells. Increased radiosensitivity was not due to impaired DNA damage signaling or repair as assessed by γ-H2AX foci formation. Instead SRP72 depletion was associated with elevated levels of apoptosis after irradiation, as measured by caspase 3/7 activity, PARP-cleavage and Annexin-V staining, and with an induction of the unfolded protein response. Together, our results show that SRP72 is a novel gene involved in radioresistance.
Author Maughan, Timothy S.
Higgins, Geoff S.
Buffa, Francesca M.
McKenna, W. Gillies
Prevo, Remko
Tiwana, Gaganpreet S.
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2017 The Author(s). Published with license by Taylor & Francis Group, LLC 2017 The Author(s)
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– notice: 2017 The Author(s). Published with license by Taylor & Francis Group, LLC 2017 The Author(s)
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Issue 6
Keywords signal recognition particle
unfolded protein response
SRP72
clonogenic assay
radiosensitivity
radiotherapy
siRNA
Apoptosis
Language English
License open-access: http://creativecommons.org/licenses/by/4.0/: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
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Snippet The identification of genetic determinants that underpin tumor radioresistance can help the development of targeted radiosensitizers or aid personalization of...
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SubjectTerms Apoptosis
Cell Survival - radiation effects
clonogenic assay
Gene Knockdown Techniques
HeLa Cells
Humans
MCF-7 Cells
Protein Biosynthesis
Radiation Tolerance
radiosensitivity
radiotherapy
Research Paper
signal recognition particle
Signal Recognition Particle - genetics
Signal Recognition Particle - metabolism
siRNA
SRP72
Unfolded Protein Response
Title Depletion of signal recognition particle 72kDa increases radiosensitivity
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