IRP2 As A Potential Modulator Of Cell Proliferation, Apoptosis And Prognosis In Non Small Cell Lung Cancer

Heena Khiroya, Jasbir Moore, Nabeel Ahmad, Jamie Kay, Kerry Woolnough, Gerald Langman, Iyad Ismail, Babu Naidu, Chris Tselepis, Alice Turner

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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.
Original languageEnglish
Article number1600711
JournalEuropean Respiratory Journal
Early online date12 Apr 2017
Publication statusPublished - 2017


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