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


Alpsoy A., GÜNDÜZ U.

TUMOR BIOLOGY, cilt.36, sa.6, ss.4417-4426, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 6
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1007/s13277-015-3081-3
  • Dergi Adı: TUMOR BIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.4417-4426
  • Anahtar Kelimeler: 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
  • Orta Doğu Teknik Üniversitesi Adresli: Evet

Özet

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.