title: Protein kinase D2 silencing reduced motility of doxorubicin-resistant MCF7 cells.
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.
authors: Department of Biological Sciences, Middle East Technical University, 06800, Ankara, Turkey.
authors: Aktan
authors: A
authors: Alpsoy
authors: Ufuk
authors: U
authors: Gündüz
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D061986:MCF-7 Cells; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000091283:Protein Kinase D2; D004317:Doxorubicin; D011494:Protein Kinases