Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri

ULUKAYA, Engin; Ari, Ferda; NAPİERALSKİ, Rudolf

Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri

Rudolf NAPİERALSKİ, (Technische Universitaet Muenchen,m rechts der Isar, Department of Obstretrics and Gynecology, Munich, Germany,)

Engin ULUKAYA (Uludag University)

Türk Biyokimya Dergisi

12 2

Yıl: 2013 Cilt: 38 Sayı: 2 Sayfa Aralığı: 154 - 162 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri

Öz:

Amaç: DNA promotör metilasyonu yoluyla gen ekspresyonunun epigenetik modülasyonu kanser hücrelerinde kemoterapiye karşı dirence neden olabilir. Bir demetile edici ajan olan desitabin (5-aza-2'-deoksisitidin) epigenetikle susturulmuş genleri yeniden aktive ederek standart kemoterapi rejimleri ile sinerjistik etki gösterebilir. Bu in vitro çalışmada, desitabin ve desitabinin antrasiklin-bazlı tedavi (FEC:5-Florourasil+Epirubisin+Siklofosfamid) ile kombinasyonunun meme kanseri hücrelerinde gen metilasyon seviyelerine etkisi araştırıldı.Metot: Desitabinin tek başına ve FEC ile kombinasyonunun farklı genlerin metilasyon seviyeleri üzerine etkisi insan MDA-MB-231 ve MCF-7 meme kanseri hücre soylarında araştırıldı. Desitabinin hücre canlılığı üzerine etkisi MTT canlılık testi ile çalışıldı. DAPK, TMS1, MGMT ve genel metilasyon göstergesi olan LINE-1 genlerinin metilasyon seviyelerini belirlemek için Methylight realtime PCR ve metilasyon spesifik PCR kullanıldı.Bulgular: LINE-1 metilasyon seviyesi desitabin ve FEC kombinasyon tedavisinden sonra her iki hücre soyunda da anlamlı olarak azaldı. MDA-MB-231 hücrelerinde, desitabin ve FEC kombinasyonunun TMS1 ve MGMT gen promotöründe metilasyon seviyelerinde azalmaya sebep olduğu gözlenirken aynı etki MCF-7 hücrelerinde gözlenmedi. Sonuç: Antrasiklin-bazlı kemoterapinin, desitabin gibi bir demetilasyon ajanı ile kombinasyonu metilasyon aracılığıyla apoptozisle ilişkili genlerin modülasyonu neden olarak kemoterapi sonucunu etkileyebilir. Daha da önemlisi, bu modülasyonun hücre tipine bağlı olarak gerçekleşebileceği görülmektedir

Anahtar Kelime:

Konular: Biyoloji Genel ve Dahili Tıp Hücre ve Doku Mühendisliği Hematoloji Biyoteknoloji ve Uygulamalı Mikrobiyoloji Genetik ve Kalıtım Hücre Biyolojisi

Changes in Gene Methylation Following Chemotherapy in Breast Cancer Cell Lines

Öz:

Objective: Epigenetic modulation of gene expression by DNA promoter methylation may contribute to acquired resistance to chemotherapy in cancer cells. Decitabine (5-aza-2’deoxycytidine), a demethylating agent, may act synergistically with standard chemotherapy regimens to activate epigenetically silenced genes. In the present in vitro study, it was investigated the effect of gene methylation level after treatment with decitabine and combination of decitabine with anthracycline-based therapeutics (5-fluorouracil plus epirubicine plus cyclophosphamide; FEC) on breast cancer cells (MCF-7 and MDA-MB-231). Methods: The effect of decitabine and its combination with FEC on different genes methylation level has been tested in MDA-MB-231 and MCF-7 human breast cancer cell lines. The effect of decitabine on the cell viability was assayed by MTT assay. Methylight real-time PCR and methylation specific PCR were carried out to determine the methylation status of certain genes: DAPK, TMS1, MGMT and the global methylation marker LINE-1.Results: The LINE-1 methylation status significantly decreased in both cell lines after treatment with the combination of decitabine with FEC. In MDA-MB-231 cells, methylation of the TMS1 and the MGMT gene promoter was significantly reduced by FEC plus decitabine while no effect was observed in MCF-7 cells. Conclusion: Anthracycline-based therapy regimens in combination with demethylating agents such as decitabine may affect chemotherapy outcome by modulation of apoptosisrelevant genes by methylation. More importantly, this modulation seems to be dependent on the cell type

Anahtar Kelime:

Konular: Biyoloji Genel ve Dahili Tıp Hücre ve Doku Mühendisliği Hematoloji Biyoteknoloji ve Uygulamalı Mikrobiyoloji Genetik ve Kalıtım Hücre Biyolojisi

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Ari F, NAPİERALSKİ R, ULUKAYA E (2013). Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. , 154 - 162.
Chicago	Ari Ferda,NAPİERALSKİ Rudolf,ULUKAYA Engin Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. (2013): 154 - 162.
MLA	Ari Ferda,NAPİERALSKİ Rudolf,ULUKAYA Engin Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. , 2013, ss.154 - 162.
AMA	Ari F,NAPİERALSKİ R,ULUKAYA E Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. . 2013; 154 - 162.
Vancouver	Ari F,NAPİERALSKİ R,ULUKAYA E Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. . 2013; 154 - 162.
IEEE	Ari F,NAPİERALSKİ R,ULUKAYA E "Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri." , ss.154 - 162, 2013.
ISNAD	Ari, Ferda vd. "Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri". (2013), 154-162.

APA	Ari F, NAPİERALSKİ R, ULUKAYA E (2013). Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. Türk Biyokimya Dergisi, 38(2), 154 - 162.
Chicago	Ari Ferda,NAPİERALSKİ Rudolf,ULUKAYA Engin Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. Türk Biyokimya Dergisi 38, no.2 (2013): 154 - 162.
MLA	Ari Ferda,NAPİERALSKİ Rudolf,ULUKAYA Engin Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. Türk Biyokimya Dergisi, vol.38, no.2, 2013, ss.154 - 162.
AMA	Ari F,NAPİERALSKİ R,ULUKAYA E Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. Türk Biyokimya Dergisi. 2013; 38(2): 154 - 162.
Vancouver	Ari F,NAPİERALSKİ R,ULUKAYA E Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri. Türk Biyokimya Dergisi. 2013; 38(2): 154 - 162.
IEEE	Ari F,NAPİERALSKİ R,ULUKAYA E "Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri." Türk Biyokimya Dergisi, 38, ss.154 - 162, 2013.
ISNAD	Ari, Ferda vd. "Meme Kanseri Hücre Soylarında Kemoterapiyi Takiben Oluşan Gen Metilasyon Değişiklikleri". Türk Biyokimya Dergisi 38/2 (2013), 154-162.