IRP2 as a potential modulator of cell proliferation, apoptosis and prognosis in nonsmall cell lung cancer

[摘要] IREB2 is a gene that produces iron regulatory protein 2 (IRP2); which is critical to intracellular iron homeostasis and which relates to the rate of cellular proliferation. IREB2 lies in a lung cancer susceptibility locus. The aims were to assess 1) the relationship between iron loading; cell proliferation and IRP2 expression in lung cancer; 2) the potential of iron related pathways as therapeutic targets; and 3) the relevance of IRP2 in operated lung cancer patients.Cells of two nonsmall cell cancer (NSCLC) lines and primary bronchial epithelial cells (PBECs) were cultured with and without iron; and proliferation; apoptosis and migration were assessed. Reverse transcriptase 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.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).Loss of iron regulation represents a poor prognostic marker in lung cancer.

[学科分类] 呼吸医学