Abstract
Background: IREB2 is a gene that produces iron regulatory protein 2 (IRP2), which is critical to intracellular iron homeostasis, which relates to rate of cellular proliferation. IREB2 lies in a lung cancer susceptibility locus.
Aims: To assess (i) Relationship between iron loading, cell proliferation and IRP2 expression in lung cancer (ii) Potential of iron related pathways as therapeutic targets (iii) Relevance of IRP2 in operated lung cancer patients.
Methods: Cells of two NSCLC lines and PBECs were cultured with and without iron; and proliferation, apoptosis and migration assessed. RT-PCR and Western blot were used to assess expression of iron homeostasis genes/proteins. Iron chelation and knockdown of IREB2 were used in vitro to explore therapeutics. A cohort of operated NSCLC patients was studied for markers of systemic iron status, tumour IRP2 staining and survival.
Results: Iron loading caused cell proliferation in cancer cell lines, which were less able to regulate IREB2 expression than PBECs. Iron chelation resulted in a return of proliferation rates to baseline levels; knockdown of IREB2 had a similar effect. IRP2 positive tumours were larger (p=0.045) and higher percentage staining related to poorer survival (p=0.079).
Conclusions: Loss of iron regulation represents a poor prognostic marker in lung cancer.
Aims: To assess (i) Relationship between iron loading, cell proliferation and IRP2 expression in lung cancer (ii) Potential of iron related pathways as therapeutic targets (iii) Relevance of IRP2 in operated lung cancer patients.
Methods: Cells of two NSCLC lines and PBECs were cultured with and without iron; and proliferation, apoptosis and migration assessed. RT-PCR and Western blot were used to assess expression of iron homeostasis genes/proteins. Iron chelation and knockdown of IREB2 were used in vitro to explore therapeutics. A cohort of operated NSCLC patients was studied for markers of systemic iron status, tumour IRP2 staining and survival.
Results: Iron loading caused cell proliferation in cancer cell lines, which were less able to regulate IREB2 expression than PBECs. Iron chelation resulted in a return of proliferation rates to baseline levels; knockdown of IREB2 had a similar effect. IRP2 positive tumours were larger (p=0.045) and higher percentage staining related to poorer survival (p=0.079).
Conclusions: Loss of iron regulation represents a poor prognostic marker in lung cancer.
| Original language | English |
|---|---|
| Article number | 1600711 |
| Journal | European Respiratory Journal |
| Volume | 49 |
| Early online date | 12 Apr 2017 |
| DOIs | |
| Publication status | Published - 2017 |
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- Khiroya_et_al_IRP2_Potential_Modulator_European_respiratory_Journal
This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication. Final Version of Record available at: http://dx.doi.org/10.1183/13993003.00711-2016