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


Alpsoy A., GÜNDÜZ U.

TUMOR BIOLOGY, vol.36, no.6, pp.4417-4426, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 6
  • Publication Date: 2015
  • Doi Number: 10.1007/s13277-015-3081-3
  • Journal Name: TUMOR BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4417-4426
  • Keywords: Multidrug resistance, Breast cancer, Migration, Protein kinase D2, BREAST-CANCER CELLS, EPITHELIAL-MESENCHYMAL TRANSITION, MULTIDRUG-RESISTANCE, INDUCED APOPTOSIS, PROSTATE-CANCER, GLIOBLASTOMA CELLS, ABC TRANSPORTERS, IN-VITRO, PROLIFERATION, EXPRESSION
  • Middle East Technical University Affiliated: Yes

Abstract

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.