RRC ID 51731
Author Miyamoto T, Kashima H, Yamada Y, Kobara H, Asaka R, Ando H, Higuchi S, Ida K, Mvunta DH, Shiozawa T.
Title Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells.
Journal PLoS One
Abstract PURPOSE:Lipocalin 2 (LCN2) is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear.
METHODS:The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV) irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively.
RESULTS:LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05). Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt) was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing.
CONCLUSIONS:These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells.
Volume 11(5)
Pages e0155220
Published 2016
DOI 10.1371/journal.pone.0155220
PII PONE-D-15-41722
PMID 27168162
PMC PMC4864227
MeSH Antineoplastic Agents / pharmacology Cell Line, Tumor Cell Movement / drug effects Cell Movement / radiation effects Cisplatin / pharmacology Cyclin-Dependent Kinase Inhibitor p21 / genetics* Cyclin-Dependent Kinase Inhibitor p21 / metabolism Drug Resistance, Neoplasm / genetics Endometrium / drug effects Endometrium / metabolism Endometrium / pathology Endometrium / radiation effects Epithelial Cells / drug effects Epithelial Cells / metabolism* Epithelial Cells / pathology Epithelial Cells / radiation effects Female Gene Expression Regulation, Neoplastic* Humans Lipocalin-2 / antagonists & inhibitors Lipocalin-2 / genetics* Lipocalin-2 / metabolism Phosphatidylinositol 3-Kinases / genetics* Phosphatidylinositol 3-Kinases / metabolism Phosphoinositide-3 Kinase Inhibitors Phosphorylation Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-akt / genetics Proto-Oncogene Proteins c-akt / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Signal Transduction Tumor Suppressor Protein p53 / genetics* Tumor Suppressor Protein p53 / metabolism Ultraviolet Rays
IF 2.776
Times Cited 11
Human and Animal Cells HHUA(RCB0658)