Fatih OLTULU, Berrin ÖZDİL, Çevik GÜREL, Eda AÇIKGÖZ, Duygu ÇALIK KOCATÜRK, Yasemin ADALI, Ayşegül UYSAL, Altuğ YAVAŞOĞLU, Gülperi ÖKTEM, Hüseyin AKTUĞ

EMG, MAPK ve inflamasyona yakından bakış: Fare embriyonik kök hücre, somatik ve kanser hücrelerinde ne farklıdır?

Amaç: Yaşam; başlangıç, hayatta kalma ve ölümü içeren hücrelerin devamlı olan döngüsünden oluşmaktadır. Hücreler devamlı olarak bölünür, farklılaşır ve somatik hücreleri oluştururlar. Somatik hücreler de belli bir noktada kanser hücrelerini oluşturup kök hücreler ile benzer karakteristikleri paylaşabilmektedirler. Bu dönemlerdeki süreçler, somatik hücrelerde anormalliğe eğilimi ve kanser hücrelerine dönüşümü tanımlamak için önemlidir. Kanserin ortaya çıkışını ve ilerleyişini kontrol etmek için, hayatta kalma mekanizmaları özellikle de epitelyal-mezenkimal geçiş (EMG) ve iltihaplanma önemlidir. EMG, hem embriyonik gelişim aşamalarında, hem de kanser ilerlemesinde ortaya çıkar ve bu süreç özellikle moleküler temelli tedavi için terapötik hedef olabilir. Gereç ve Yöntem: EMG, MAP-Kinaz ve inflamasyon yolaklarının gen ekspresyon seviyesinde karşılaştırılmasında kanser hücreleri temsili için fare skuamöz akciğer kanseri hücreleri (SqLCCs), somatik kökenli hücre örneği olarak fare derisi fibroblastları (MSF'ler) ve embriyonik kök hücre olarak da fare embriyonik kök hücreleri (mEKH'ler) kullanılmıştır. ERK 1/2, Vimentin ve Twist'in immünofloresan boyama protein düzeyleri aynı hücrelerde karşılaştırılarak incelenmiştir. Bulgular: MSF'lerde ve SqLCC'lerde ERK1/2 protein ekspresyonu benzer iken mEKH’lerde ekspresyonu en düşük bulunmuştur. Ayrıca, Twist ve Vimentin ifadesi istatistiksel olarak üç hücre hattında farklı çıkmıştır. EMG'nin gen ekspresyon profiline ve MAPK sinyal yolağının desteklediği inflamasyona göre, özellikle Sparc, Vimentin, Mapksp1 ve Il24 gibi belirgin genlerde ekspresyon profilleri birbirinden çok farklı bulunmuştur. Sonuç: Üç farklı hücre hattı hem gen hem de protein ekspresyonunda farklı özellikler göstermiştir. Bu nedenle, bu moleküller terapötik hedef belirlenmesinde potansiyel itici güç olabilir.

Anahtar Kelimeler:

Kanser, Epitelyal mezenkimal geçiş, inflamasyon, MAPK, Embriyonik kök hücre

CLOSE LOOK IN EMT, MAPK AND INFLAMMATION: WHAT DIFFERS BETWEEN MOUSE EMBRYONIC STEM, SOMATIC AND CANCER CELLS?

Objective: Life is a continuous cycle of the cells, composed of beginning, surviving and death. Cells keep dividing, differentiate and turn into somatic cells. The somatic cells at some point can give way to cancer cells and share characteristics of stem cells. The processes during these periods are important for identifying the tendency to abnormality and transformation to the cancer cells in somatic cells. To control emergence and progress of the cancer, mechanisms which take part in the survival become significant, especially EMT and inflammation. EMT occurs in both embryonic developmental stages and cancer progression and molecular basis of this process can be the therapeutic target for cure. Material and Method: For cancer representation mouse squamous lung cancer cells (SqLCCs), for somatic origin mouse skin fibroblasts (MSFs) and for embryonic stem cell mouse embryonic stem cells (mESCs) were used for comparison of three signaling pathways (EMT, MAPK and inflammation) at the gene expression level. Immunofluorescence staining protein levels of ERK 1/2, Vimentin and Twist were compared. Results: ERK1/2 protein expression similar in MSFs and SqLCCs while mESCs expression wasthe lowest. Besides, Twist and Vimentin expression statistically different in three. According to gene expression profiling of the EMT and inflammation supported by the MAPK signaling pathway are a far cry from each other at prominent genes especially Sparc, Vimentin, Mapksp1 and Il24.

Keywords:

Cancer, epithelial- mesenchymal transition, inflammation, MAPK, embryonic stem cell,

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