Protein kinase D2 silencing reduced motility of doxorubicin-resistant MCF7 cells

Alpsoy, Aktan
Gündüz, Ufuk
Success of chemotherapy is generally impaired by multidrug resistance, intrinsic resistance, or acquired resistance to functionally and structurally irrelevant drugs. Multidrug resistance emerges via distinct mechanisms: increased drug export, decreased drug internalization, dysfunctional apoptotic machinery, increased DNA damage repair, altered cell cycle regulation, and increased drug detoxification. Several reports demonstrated that multidrug resistance is a multifaceted problem such that multidrug resistance correlates with increased aggressiveness and metastatic potential. Here, we tested the involvement of protein kinase D2, a serine/threonine kinase that was previously implicated in proliferation, drug resistance, and motility in doxorubicin-resistant MCF7 (MCF7/DOX) cell line, which served as an in vitro model for drug resistance and invasiveness. We showed that basal level activity of protein kinase D2 (PKD2) was higher in MCF7/DOX cells than parental MCF7 cells. To elucidate the roles of PKD2 MCF7/DOX, PKD2 expression was reduced via small interfering RNA (siRNA)-mediated knockdown. Results showed that acquired resistance of MCF7/DOX to doxorubicin was not affected by PKD2 silencing, while motility of MCF7/DOX cells was reduced. The results implied that PKD2 silencing might inhibit migration of MCF7/DOX cells without affecting chemoresistance significantly.


Drug resistant MCF-7 cells exhibit epithelial-mesenchymal transition gene expression pattern
Iseri, Ozlem Darcansoy; Kars, Meltem Demirel; Arpaci, Fikret; Atalay, Can; Pak, Isin; Gündüz, Ufuk (2011-02-01)
Purpose: Multidrug resistance is resistance to structurally unrelated anticancer agents. Large-scale expression analysis by using high-density oligonucleotide microarrays may provide information about new candidate genes contributing to MDR. This study demonstrates alterations in expression levels of several genes related to epithelial-mesenchymal transition (EMT) in paclitaxel, docetaxel, and doxorubicin resistant MCF-7 cells.
Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance
Kaplan, Esra; Gündüz, Ufuk (2012-02-01)
Purpose: Development of resistance against anti-cancer drugs is one of the major obstacles of chemotherapy in the treatment of cancer. Etoposide is a topoisomerase II alpha (TOP2A) inhibitor, which is used in the treatment of breast cancer. Alterations in the expression of drug targets or DNA repair genes are among the important resistance mechanisms against TOP2A inhibitors. In this study, expression changes in TOP2A gene and two important mismatch repair (MMR) genes MSH2 and MLH1 were examined in order to...
Reversal of multidrug resistance in mcf-7 breast adenocarcinoma cell line by silencing interleukin 6 with RNA interference
Çakmak, Neşe; Gündüz, Ufuk; Department of Biology (2013)
Multidrug resistance (MDR) in cancer is characterized by development of resistance to several unrelated drugs upon long time administration of a certain type of chemotherapeutic agent. In doxorubicin resistant MCF-7 cell line, resistance is developed mainly by upregulation of MDR1 gene which encodes an ABC transporter protein known as P-glycoprotein. Interleukin 6 (IL-6) is a cytokine which acts as a growth factor for certain cell types including some cancer cells. IL-6 is found at high levels in cancer pat...
Etoposide resistance in MCF-7 breast cancer cell line is marked by multiple mechanisms
Alpsoy, Aktan; Yasa, Seda; Gündüz, Ufuk (2014-04-01)
Purpose: Acquired or intrinsic drug resistance is one of the major handicaps in the success of chemotherapy. Etoposide is a topoisomerase II poison widely used in chemotherapy. Similar to other topoisomerase inhibitors and DNA damaging agents, resistance to etoposide may arise as a result of alterations in target expression and activity, increased drug efflux and alterations in DNA damage response mechanisms. Here, we tested the involvement of such mechanisms in etoposide-resistant MCF-7 breast cancer cells.
Development and investigation of etoposide resistance in MCF-7 Breast cancer cell line
Kaplan, Esra; Gündüz, Ufuk; Department of Biology (2010)
Failure of chemotherapy in cancer patients because of development of drug resistance is a major problem. Alterations of DNA repair mechanisms and drug targets are among the important resistance mechanisms which are developed against topoisomerase II inhibitors etoposide and doxorubicin. Modifications in the expression levels of mismatch repair (MMR) genes due to resistance to topoisomerase II inhibitors are involved in breast cancer. In this study, etoposide resistant sublines were developed from MCF7 breas...
Citation Formats
A. Alpsoy and U. Gündüz, “Protein kinase D2 silencing reduced motility of doxorubicin-resistant MCF7 cells,” TUMOR BIOLOGY, pp. 4417–4426, 2015, Accessed: 00, 2020. [Online]. Available: