Year 2018, Volume 57 , Issue 1, Pages 36 - 45 2018-03-01

Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells
Meme kanseri kanser kök hücrelerinde PD-0332991 uygulanmasının hücre döngüsü düzenleyici genler üzerine etkisi

Hasan ONUR ÇAĞLAR [1] , Sunde YILMAZ SÜSLÜER [2] , Cumhur GÜNDÜZ [3] , Ayfer HAYDAROĞLU [4]


Aim: Palbociclib (PD-0332991) is an inhibitor for cyclin-dependent kinase 4/6 complex and exhibits more activity in luminal ER+ breast cancer. However, sensitivity of breast cancer stem cells (BCSCs) to PD-0332991 treatment and expression patterns of cell cycle regulatory genes after PD-0332991 treatment in BCSCs are still unclear. This study aims to determine response of BCSCs to PD-0332991 treatment.

Materials and Methods: An experimental in vitro study was designed on breast cancer cell lines. MCF-7 and BCSCs cell lines were used in this study. Water soluble tetrazolium salt-1 (WST-1) test was used for the cytotoxicity assay. Cell cycle distribution pattern and apoptosis were examined with flow cytometry according to IC50 values at 48th h. Real-Time PCR was used to detect expression profiles of CDKN1A, CHEK1, CDKN2A, CDC25A, and CCND1 genes.

Results: PD-0332991 decreased cell proliferation in both cell lines. G0/G1 arrest was detected for both cell lines. There was no apoptotic effect of PD-0332991 on MCF-7 cells and BCSCs. In MCF-7 cells, expression levels of CDKN1A, CDKN2A, and CCND1 genes were increased as 3.11, 3.21, and 1.05 folds, respectively. Expression levels of CHEK1 and CDC25A genes were decreased as 4.75 and 3.73 folds, respectively. In BCSCs, expression levels of CDKN1A, CHEK1, CDKN2A, and CCND1 were decreased as 1.15, 2.01, 1.32, and 1.68 folds, respectively. No expression of CDC25A gene was found in BCSCs group.

Conclusion: In this study, it was observed that PD-0332991 leads to different expression profiles for cell cycle regulatory genes between BCSCs and breast cancer cells.

Amaç: Palbociclib (PD-0332991) siklin bağımlı kinaz 4/6 kompleksi için bir inhibitördür ve luminal ER+ meme kanserlerinde daha fazla aktivite sergilemektedir. Ancak, meme kanseri kök hücrelerinin (MKKH) PD-0332991 uygulamasına olan hassasiyeti ve hücre döngüsü düzenleyici genleri üzerine PD-0332991’in etkisi MKKH’leri için açıklığa kavuşmamıştır. Bu çalışma, MKKH’lerinin PD-0332991 uygulamasına olan yanıtın belirlenmesini amaçlamaktadır.

Gereç ve Yöntem: Meme kanseri hücre hatları üzerinde deneysel bir in vitro çalışma tasarlanmıştır. Bu çalışmada, MCF-7 ve MKKH hücre hatları kullanıldı. Suda çözünür tetrazolyum tuzu-1 (WST-1) testi sitotoksisite deneyi için kullanıldı. Hücre döngüsü dağılımı ve apoptosis, 48. saat IC50 değerlerine göre flow sitometri ile incelendi. CDKN1A, CHEK1, CDKN2A, CDC25A ve CCND1 genlerinin ifade profillerinin belirlenmesinde Real-Time PCR kullanıldı.

Bulgular: Her iki hücre hattında, PD-0332991 hücre proliferasyonunu azalttı. Her iki hücre hattı için G0/G1 tutuklanması belirlendi. PD-0332991’in apoptotik etkisi MCF-7 ve MKKH hücrelerinde bulunmadı. MCF-7 hücrelerinde, CDKN1A, CDKN2A ve CCND1 ifade düzeyleri sırasıyla 3,11; 3,21 ve 1,05 kat arttı. CHEK1 ve CDC25A ifade düzeyleri sırasıyla 4,75 ve 3,73 kat azaldı. MKKH’lerinde CDKN1A, CHEK1, CDKN2A ve CCND1 ifade düzeleri sırasıyla 1,15; 2,01; 1,32 ve 1,68 kat azaldı. MKKH’lerinde, CDC25A geni ifadesi bulunmadı.

Sonuç: Bu çalışmada, MKKH ve meme kanseri hücreleri arasında PD-0332991’in hücre döngüsü düzenleyici genler için farklı ifade profillerine neden olduğu gözlenmiştir.

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Primary Language en
Subjects Health Care Sciences and Services
Journal Section Research Articles
Authors

Orcid: 0000-0002-3637-4755
Author: Hasan ONUR ÇAĞLAR (Primary Author)
Country: Turkey


Orcid: 0000-0002-0535-150X
Author: Sunde YILMAZ SÜSLÜER
Institution: Ege University Faculty of Medicine, Department of Medical Biology, İzmir
Country: Turkey


Orcid: 0000-0002-6593-3237
Author: Cumhur GÜNDÜZ
Institution: Ege University Faculty of Medicine, Department of Medical Biology, İzmir
Country: Turkey


Orcid: 0000-0001-5709-0981
Author: Ayfer HAYDAROĞLU
Institution: EGE ÜNİVERSİTESİ, TIP FAKÜLTESİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, RADYASYON ONKOLOJİSİ ANABİLİM DALI
Country: Turkey


Dates

Application Date : August 22, 2016
Acceptance Date : February 28, 2018
Publication Date : March 1, 2018

Bibtex @research article { etd414615, journal = {Ege Tıp Dergisi}, issn = {1016-9113}, eissn = {2147-6500}, address = {}, publisher = {Ege University}, year = {2018}, volume = {57}, pages = {36 - 45}, doi = {10.19161/etd.414615}, title = {Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells}, key = {cite}, author = {Onur Çağlar, Hasan and Yılmaz Süslüer, Sunde and Gündüz, Cumhur and Haydaroğlu, Ayfer} }
APA Onur Çağlar, H , Yılmaz Süslüer, S , Gündüz, C , Haydaroğlu, A . (2018). Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells . Ege Tıp Dergisi , 57 (1) , 36-45 . DOI: 10.19161/etd.414615
MLA Onur Çağlar, H , Yılmaz Süslüer, S , Gündüz, C , Haydaroğlu, A . "Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells" . Ege Tıp Dergisi 57 (2018 ): 36-45 <http://egetipdergisi.com.tr/en/pub/issue/36515/414615>
Chicago Onur Çağlar, H , Yılmaz Süslüer, S , Gündüz, C , Haydaroğlu, A . "Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells". Ege Tıp Dergisi 57 (2018 ): 36-45
RIS TY - JOUR T1 - Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells AU - Hasan Onur Çağlar , Sunde Yılmaz Süslüer , Cumhur Gündüz , Ayfer Haydaroğlu Y1 - 2018 PY - 2018 N1 - doi: 10.19161/etd.414615 DO - 10.19161/etd.414615 T2 - Ege Tıp Dergisi JF - Journal JO - JOR SP - 36 EP - 45 VL - 57 IS - 1 SN - 1016-9113-2147-6500 M3 - doi: 10.19161/etd.414615 UR - https://doi.org/10.19161/etd.414615 Y2 - 2018 ER -
EndNote %0 Ege Tıp Dergisi Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells %A Hasan Onur Çağlar , Sunde Yılmaz Süslüer , Cumhur Gündüz , Ayfer Haydaroğlu %T Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells %D 2018 %J Ege Tıp Dergisi %P 1016-9113-2147-6500 %V 57 %N 1 %R doi: 10.19161/etd.414615 %U 10.19161/etd.414615
ISNAD Onur Çağlar, Hasan , Yılmaz Süslüer, Sunde , Gündüz, Cumhur , Haydaroğlu, Ayfer . "Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells". Ege Tıp Dergisi 57 / 1 (March 2018): 36-45 . https://doi.org/10.19161/etd.414615
AMA Onur Çağlar H , Yılmaz Süslüer S , Gündüz C , Haydaroğlu A . Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells. ETD. 2018; 57(1): 36-45.
Vancouver Onur Çağlar H , Yılmaz Süslüer S , Gündüz C , Haydaroğlu A . Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells. Ege Tıp Dergisi. 2018; 57(1): 36-45.
IEEE H. Onur Çağlar , S. Yılmaz Süslüer , C. Gündüz and A. Haydaroğlu , "Influence of PD-0332991 treatment on cell cycle regulatory genes in breast cancer stem cells", Ege Tıp Dergisi, vol. 57, no. 1, pp. 36-45, Mar. 2018, doi:10.19161/etd.414615

Authors of the Article
Hasan ONUR ÇAĞLAR [1]
Sunde YILMAZ SÜSLÜER [2]
Cumhur GÜNDÜZ [3]
Ayfer HAYDAROĞLU [4]