Hypoxia and Cancer

Abstract

A decrease in the required oxygen level in the tissue below the normal value is defined as hypoxia. Hypoxia is a common condition in solid tumors. When tumor cells can not get enough oxygen, they adapt to the hypoxic state by creating genetic differences before going to cell death. Hypoxia has been shown to play a role in developing radio or chemotherapeutic treatment resistance in some tumors. As a result of many clinical studies, it has been demonstrated that the tumor is hypoxic, and the diameter of the tumor increases with a hypoxic state. As a result of the decreased sensitivity of tumor cells to cell death signals and apoptosis, tumor cells can become regionally and systemically aggressive. Also, hypoxia can increase tumor proliferation, angiogenesis, and systemic metastasis signaling. The main protein family responsible for the molecular mechanism of hypoxia in cells is HIF (Hypoxia Inducible Factor). To date, three HIF family members have been identified in response to low oxygen levels in human cells. Named as HIF-1, HIF-2 and HIF-3, each of these heterodimers consists of α subunit and β subunit decomposing under normoxic conditions. Members of the HIF family facilitate both oxygen delivery and adapta-tion to oxygen deprivation by regulating the expression of genes involved in many cellular processes, including glucose uptake and metabolism, erythropoiesis, angiogenesis, cell proliferation, and apoptosis. This review summa-rizes the molecular working mechanism of HIF, the biological functions of hypoxia, and different hypoxia models used in cell culture laboratories.

Keywords

• Hypoxia
• Cancer
• HIF
• Experimental hypoxia
• Chemical hypoxia

Hipoksi ve Kanser

Abstract

Dokudaki gerekli oksijen seviyesinin normal değerin altına düşmesi hipoksi olarak tanımlanır. Hipoksi katı tümör-lerde sık karşılaşılan bir durumdur. Tümör hücreleri yeterli oksijen alamadığında hücre ölümüne gitmeden önce genetik farklılıklar oluşturarak hipoksik duruma adapte olmaktadır. Bazı tümörlerde radyo veya kemoterapötik tedavi direncinin gelişiminde hipoksinin rol oynadığı gösterilmiştir. Birçok klinik çalışma sonucunda tümörün hipoksik olduğu ve hipoksik durumun yükselmesiyle de tümör çapının arttığı gösterilmiştir. Hipoksik hale gelen tümör hücrelerinin, hücre ölüm sinyallerine ve apoptoza karşı duyarlılığının azalması sonucu bölgesel ve sistemik olarak agresif olabilmektedir. Ayrıca hipoksi; tümör proliferasyonu, anjiyogenez ve sistemik metastaz sinyalizasy-onunu arttırabilmektedir. Hücrelerdeki hipoksinin moleküler mekanizmasından sorumlu temel protein ailesi HIF (Hipoksi ile İndükelenebilir Faktör)’ dir. Bugüne kadar, insan hücrelerinde düşük oksijen seviyelerine yanıt olarak üç HIF protein ailesi üyesi tespit edilmiştir. HIF-1, HIF-2 ve HIF-3 olarak isimlendirilen bu heterodimerlerin her birisi, normoksik koşullarda ayrışan α alt birim ve β alt birimden oluşan proteinlerdir. HIF ailesi üyeleri glikoz alımı ve metabolizması, eritropoez, anjiyogenez, hücre proliferasyonu ve apoptoz dahil olmak üzere birçok hücresel süreçte yer alan genlerin ifadesini düzenleyerek hem oksijen dağıtımını hem de oksijen yoksunluğuna adaptasyonu kolaylaştırırlar. Bu derleme, HIF’ in moleküler çalışma mekanizmasını, hipoksinin biyolojik fonksiyonlarını ve hücre kültürü laboratuarlarında kullanılan farklı hipoksi modellerini özetlemektedir.

Keywords

• Deneysel hipoksi
• HIF
• Kanser
• Kimyasal Hipoksi

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