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Analysis of Chromat...
Analysis of Chromatin Opening in Heterochromatic Non-Small Cell Lung Cancer Tumor-Initiating Cells in Relation to DNA-Damaging Antitumor Treatment
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- Eriksson, Mina (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Hååg, Petra (author)
- Karolinska Institutet
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- Brzozowska, Beata (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,University of Warsaw, Poland
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Lipka, Magdalena (author)
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Lisowska, Halina (author)
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- Lewensohn, Rolf (author)
- Karolinska Institutet
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- Wojcik, Andrzej (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Jan Kochanowski University, Poland
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- Viktorsson, Kristina (author)
- Karolinska Institutet
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- Lundholm, Lovisa (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English.
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In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 100:1, s. 174-187
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Purpose: We previously reported that sphere-forming non-small cell lung cancer (NSCLC) tumor-initiating cells (TICs) have an altered activation of DNA damage response-and repair proteins and are refractory to DNA-damaging treatments. We analyzed whether chromatin organization plays a role in the observed refractoriness.Methods and Materials: Bulk cells and TICs from the NSCLC H23 and H1299 cell lines were examined using cell viability, clonogenic survival, Western blot, short interfering RNA analysis, and micronucleus assay.Results: NSCLC TICs displayed elevated heterochromatin markers trimethylated lysine 9 of histone H3 and heterochromatin protein 1 gamma relative to bulk cells and reduced cell viability upon histone deacetylase inhibition (HDACi). Vorinostat and trichostatin A increased the euchromatin markers acetylated lysine 9/14 of histone H3 and lysine 8 of histone H4, and HDACi pretreatment increased the phosphorylation of the DNA damage response proteins ataxia telangiectasia mutated and DNA-dependent protein kinase, catalytic subunit, upon irradiation in TICs. HDACi sensitized TICs to cisplatin and to some extent to ionizing irradiation. The protectiveness of a dense chromatin structure was indicated by an enhanced frequency of micronuclei in TICs following irradiation, after knockdown of heterochromatin protein 1 gamma.Conclusions: Although confirmatory studies in additional NSCLC model systems and with respect to analyses of other DNA damage response proteins are needed, our data point toward a heterochromatic structure of NSCLC TICs, such that HDACi can sensitize TICs to DNA damage.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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