Calzolari Alessia, Finisguerra Veronica, Oliviero Isabella, Deaglio Silvia, Mariani Gualtiero, Malavasi Fabio, Testa Ugo
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Blood Cells Mol Dis. 2009 Jan-Feb;42(1):5-13. doi: 10.1016/j.bcmd.2008.10.001. Epub 2008 Nov 18.
In a recent study we have explored TfR2 expression in a panel of cancer cell lines and we observed that about 40% of these cell lines clearly express TfR2. Taking advantage of this observation and considering the frequent overexpression of c-Myc in cancer cells we have explored the existence of a possible relationship between c-Myc and TfR2 in these cell lines. Our results provided evidence that TfR2(+) cell lines express low c-Myc levels and low TfR1 levels, while TfR2(-) cell lines express high c-Myc and TfR1 levels. Using the erythroleukemic K562 TfR2(+) cells as a model, we observed that agents that enhance c-Myc expression, such as iron, determine a decrease of TfR2 expression, while molecules that induce a decreased c-Myc expression, such as the iron chelator desferoxamine or the kinase inhibitor ST 1571, induce an enhanced TfR2 expression. On the other hand, we have evaluated a possible effect of hypoxia and nitric oxide on TfR2 expression in erythroleukemia K526 and hepatoma HepG2 cells, providing evidence that: (i) agents inducing cellular hypoxia, such as CoCl(2), elicited a marked upmodulation of TfR1, but a downmodulation of TfR2 expression; (ii) NO(+) donors, such as sodium nitroprusside (SNP), induced a moderate decrease of TfR1, associated with a marked decline of TfR2 expression; (iii) NO donors, such as S-Nitroso-N-Acetylpenicillamine (SNAP), induced a clear increase of TfR1, associated with a moderate upmodulation of TfR2 expression. The ensemble of these observations suggests that in cancer cell lines TfR2 expression can be modulated through stimuli similar to those known to act on TfR1 and these findings may have important implications for our understanding of the role of TfR2 in the regulation of iron homeostasis.
在最近的一项研究中，我们在一组癌细胞系中探究了转铁蛋白受体2（TfR2）的表达情况，并且观察到约40%的这些细胞系明显表达TfR2。利用这一观察结果，并考虑到癌细胞中c-Myc的频繁过表达，我们探究了在这些细胞系中c-Myc与TfR2之间可能存在的关系。我们的结果表明，TfR2（+）细胞系表达低水平的c-Myc和低水平的转铁蛋白受体1（TfR1），而TfR2（-）细胞系表达高水平的c-Myc和TfR1。以红白血病K562 TfR2（+）细胞为模型，我们观察到增强c-Myc表达的试剂，如铁，会导致TfR2表达下降，而诱导c-Myc表达降低的分子，如铁螯合剂去铁胺或激酶抑制剂ST 1571，则会诱导TfR2表达增强。另一方面，我们评估了缺氧和一氧化氮对红白血病K526和肝癌HepG2细胞中TfR2表达的可能影响，结果表明：（i）诱导细胞缺氧的试剂，如氯化钴（CoCl₂），会引起TfR1的显著上调，但TfR2表达下调；（ii）一氧化氮供体，如硝普钠（SNP），会诱导TfR1适度下降，同时TfR2表达显著下降；（iii）一氧化氮供体，如S-亚硝基-N-乙酰青霉胺（SNAP），会诱导TfR1明显增加，同时TfR2表达适度上调。这些观察结果总体表明，在癌细胞系中，TfR2的表达可以通过类似于已知作用于TfR1的刺激来调节，这些发现可能对我们理解TfR2在铁稳态调节中的作用具有重要意义。
