Downregulation of Programmed Cell Death 10 (PDCD 10) Expression Confers Doxorubicin Resistance in Breast Cancer Cells

Date

2017-10-08

Author

Mamatoğlu, Çağrı Urfalı
Kazan, Hasan Hüseyin
Gündüz, Ufuk

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Dysregulated apoptosis is one of the major drug resistance mechanisms. Programmed cell death 10 (PDCD10) is a novel apoptosis regulator, involving in modulation of apoptosis and cell survival. Despite its importance in apoptotic regulation, the role of PDCD10 in drug resistance has not been understood yet. We screened parental and doxorubicin-resistant MCF7, HeLa and K562 cells for PDCD10 expression. Our results showed that PDCD10 expression is cell-specific; significantly downregulated in MCF7 and upregulated in HeLa whereas there is no significant alteration in K562 cell line when the parental cells acquire resistance to doxorubicin. Transient downregulation of PDCD10 expression resulted in 3 fold increase in IC value of doxorubicin, leading to enhanced resistance in MCF7 cell line. 50 Similarly, overexpression of PDCD10 partially resensitized drug-resistant MCF7 cells to doxorubicin. PDCD10-downregulated parental MCF7 cells were shown to be resistant to apoptosis when exposed to apoptosis inducer, etoposide. Expression levels of anti-apoptotic BCL2 and Survivin increased after PDCD10 silencing, resembling the gene expression pattern of doxorubicin-resistant subline. Moreover, inhibition of PDCD10 expression in MCF7 cell line aggressiveness and led to higher cellular motility which is a characteristic attributed to doxorubicin-resistant cells. Our study showed that PDCD10 expression is cell-specific and inhibition of PDCD10 expression enables doxorubicin resistance in MCF7 breast cancer cells

Subject Keywords

Multidrug resistance, Apoptosis, PDCD10

URI

https://hdl.handle.net/11511/85772

Conference Name

MolBioKon’17, (8 - 10 Eylül 2017)

Collections

Graduate School of Natural and Applied Sciences, Conference / Seminar

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Citation Formats

Ç. U. Mamatoğlu, H. H. Kazan, and U. Gündüz, “Downregulation of Programmed Cell Death 10 (PDCD 10) Expression Confers Doxorubicin Resistance in Breast Cancer Cells,” presented at the MolBioKon’17, (8 - 10 Eylül 2017), İstanbul, Türkiye, 2017, Accessed: 00, 2021. [Online]. Available: https://hdl.handle.net/11511/85772.