Ndrg1’in kanser ve demir şelatörleri ile ilişkisi

Year 2013, Volume: 30 Issue: 1s, 33 - 37, 28.11.2013

Osman Salış Abdülkerim Bedir Hasan Alaçam

Abstract

İnsan N-myc downstream-regulated gene1 (Ndrg1), ilk olarak Charcot-Marie-Tooth tip 4D (CMT4D) hastalığında tanımlanmıştır. Son zamanlarda ise hücre diferansiyasyonu,
proliferasyon ve büyümenin baskılanması, neoplazi, tümör progresyonu ve metastaz ile ilişkisi ortaya konulmuştur. Ndrg1 geni, farklı kanser türlerinde farklı şekilde etkilenmektedir. Meme, prostat, kolon kanseri gibi kanserlerde downregule iken, karaciğer kanserlerinde upregüle’dir. Ndrg1 geninin düzenlenmesinde farklı hücre tiplerinde farklı ve kompleks mekanizmalar rol alabilmektedir. Bu kompleks düzenlemeler, transkripsiyonel, posttranskripsiyonel ve translasyonal seviyelerdeki major yolları içerir. Yapılan çalışmalarda desferoksamin (DFO) ve diğer şelatörlerin etkili anti-tümör ajanlar oldukları gösterilmiştir. Şelatörler bu etkilerini muhtemelen Ndrg1 mRNA transkripsiyonunu etkileyerek göstermektedir. Ancak bu regülasyonun hangi mekanizma ile oluştuğu net değildir ve demirin gen ekspresyonu ve proliferasyondaki rolünü irdelerken Ndrg1’in daha fazla araştırılması gerekmektedir.

Association of Ndrg-1 with cancer and iron chelators

Human N-myc downstream-regulated gene 1 (Ndrg-1) has been first identified in Charhot-Marie-Tooth Disease type 4D (CMT4D). Recently, its association with cell differentiation, suppression of growth and proliferation, neoplasia, tumor progression and metastasis has been demonstrated. Ndrg-1 gene appears to be regulated in a variety of ways in different types of cancers. It is down-regulated in breast, prostate and colon cancers whereas it is up-regulated in hepatic cancers. Different and complex mechanisms may play a role in different types of cells in regulation of Ndrg-1 gene. These complex regulations includes major pathways in transcriptional, post-transcriptional and translational levels. It has been shown that desferrioxamine (DFO) and other chelators are effective anti-tumor agents. It’s possible that this effect of chelators is related to Ndrg-1 mRNA transcription, but it remains unknown which mechanism mediates this regulation and iron’s role in gene expression and proliferation and Ndrg-1 need further investigations.

Keywords

Demir; desferoksamin; diferansiyasyon; HIF-1; kanser; Ndrg-1 (Iron; desferrioxamine; differentiation; HIF-1; cancer; Ndrg-1)

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