Farklı Hücre Hatlarında Hipoksik Koşullarda ADAMTS-2 İfadesinin Değişimi

Year 2019, , 22 - 33, 28.05.2019

Sümeyye Aydogan Türkoğlu , Sinem Gültekin Tosun Feray Köçkar

https://doi.org/10.35414/akufemubid.428822

Cited By: 1

Abstract

ADAMTS’ler (A Disintegrin And Metalloproteaz With
Trombospondin Motifs; Trombospondin Motifli Matriks Metalloproteazlar)
dokuların yeniden düzenlenmesi, matriks yapımı ve yıkımı gibi fizyolojik
olaylarda rol aldığı gibi kanser, kas-iskelet sistemi hastalıkları,
enflamasyon, fibrozis gibi patolojik olaylarda da yer alır. ADAMTS ailesine ait
19 üye tanımlanmış ve birçok özelliğine göre gruplandırılmıştır. Bu gruplardan
ADAMTS2, 3 ve 14 kollajen ADAMTS’ leri oluşturur ve kollajen işlenmesinde görev
alır. ADAMTS2’nin önemli özelliklerinden biri kollajenlerin amino uçlarının
kesilip uzaklaştırılmasında görev alması yeni tespit edilen diğer bir
fonksiyonu  ise anti-anjiyogenik
aktiviteye sahip olmasıdır. Hipoksik
regülasyon hücresel düzeyde çok sayıda genin ifadesini etkileyen bir süreçtir.
Hücrelerde meydana gelen hipoksiya ile başta HIF-1 olmak üzere birçok gen
aktive olur. HIF-1 hücresel oksijen konsantrasyonundaki değişimleri algılayarak yanıt oluşturmadan sorumlu transkripsiyon faktörüdür.
Çalışmamızda ilk kez ADAMTS2 geninin hipoksik regülasyonu çalışılmış ve farklı
hücre hatlarında hipoksik koşullardaki değişimi mRNA seviyesinde tespit
edilmiştir. Çalışmamız
kapsamında Saos-2, MG-63 (insan kemik karsinomu), PC-3, DU-145 (insan prostat
karsinomu), MCF-7 (insan meme karsinomu), HT29, Colo-205 (insan kolon
karsinomu), MKN-45 (insan gastrik karsinomu), Panc-1, Mia PaCa-2 (insan
pankreas karsinomu), K-562 (insan kronik myeloid lösemi hücresi) ve HUVEC
(insan umblikal ven endotel hücresi) hücre hatları seçilmiş ve yapılan
analizlere göre ADAMTS2’ nin  en çok
MG-63 kemik karsinomda ifade olduğu tespit edilmiştir. Mia PaCa-2 ve K-562
hücrelerinde ise tespit edilebilir düzeyde ekspre olmadığı belirlenmiştir.
Kimyasal hipoksi modeli oluşturulmuş ve ADAMTS2 
mRNA seviyesi farklı hücre hatlarında incelenmiştir. DU-145, PC-3,
HT-29, MCF-7 ve Saos-2 hücre hatlarında mRNA düzeyinde ADAMTS2 seviyesinin
hipoksiyada arttığı tespit edilmiştir. En yüksek hipoksik cevap Saos-2 ve MCF-7
hücrelerinde gözlenmiştir.

Keywords

ADAMTS-2, Kollajen, Hipoksi, Anjiyogenez, Hücre Hattı

Variation of ADAMTS-2 Gene Expression in Hypoxic Conditions in Different Cell Lines

Abstract

ADAMTS
(A Disintegrin And Metalloproteinase with Trombospondin Motifs) is involved in
pathological events such as cancer, fibrosis, musculoskeletal disorders,
inflamation as well as physiological events such as tissue reorganization,
matrix building and destruction. 19 members of the ADAMTS family have been
identified and grouped according to many characteristics. The important
features of ADAMTS2 is processing the amino ends of the collagen and also has
an anti-angiogenic activity. Hypoxic
regulation is a process that affects the expression of many genes at the
cellular level. Hypoxia activates many genes, mainly HIF-1 transcription factor
which is responsible for detecting changes in cellular
oxygen concentration and for generating responses. For the first time, the
hypoxic regulation of ADAMTS2 gene was studied and the variation in hypoxic
conditions was determined at the mRNA level using different cell lines. We evaluated the effects of hypoxia in the
expression level of ADAMTS-2 in different cell lines namely; Saos-2, MG-63
(bone carcinoma), PC-3, DU-145 (prostate carcinoma), MCF-7 (breast carcinoma),
HT29, Colo-205 (colon carcinoma), MKN-45 (gastric carcinoma), Panc-1, Mia
PaCa-2 (pancreatic carcinoma), K-562 (chronic myeloid leukemia cell) and HUVEC
(umbilical vein endothelial cell). We found the most expression level in MG-63.
Mia PaCa-2 and K-562 cells were not expressed detectable
level of ADAMTS-2. A chemical hypoxic model was constructed and the level of
ADAMTS2 mRNA was examined. It has been
determined that ADAMTS2 mRNA level is increased in hypoxia in DU-145, PC-3,
HT-29, MCF-7 and Saos-2 cells.
The highest hypoxic response was observed in Saos-2 and MCF-7 cells.

Keywords

ADAMTS-2, Collagene, Hypoxia, Angiogenesis, Cell Line

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