RRC ID 67300
Author Abe S, Yamamoto K, Kurata M, Abe-Suzuki S, Horii R, Akiyama F, Kitagawa M.
Title Targeting MCM2 function as a novel strategy for the treatment of highly malignant breast tumors.
Journal Oncotarget
Abstract Highly malignant tumors express high levels of the minichromosome maintenance 2 (MCM2) protein, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In a previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70 bound MCM2, impaired its nuclear translocation, and enhanced DNA-damage-induced apoptosis in FLV-infected hematopoietic cells when the cells expressed high levels of MCM2. Here, we show that MCM2 is highly expressed in clinical samples of invasive carcinoma of the breast, especially triple-negative breast cancer (TNBC), and in cancer stem cell (CSC) marker-positive breast cancer cells. To generate a cancer therapy model using gp70, we introduced the gp70 protein into the cytoplasm of murine breast cancer cells that express high levels of MCM2 by conjugating the protein transduction domain (PTD) of Hph-1 to gp70 (Hph-1-gp70). Hph-1-gp70 was successfully transduced into the cytoplasm of breast cancer cells. The transduced protein enhanced the DNA damage-induced apoptosis of cancer cells in vitro and in vivo. Therefore, an MCM2-targeted strategy using Hph-1-gp70 treatment to induce DNA damage might be a successful therapy for highly malignant breast cancers such as TNBC and for the eradication of CSC-like cells from breast cancer tissue.
Volume 6(33)
Pages 34892-909
Published 2015-10-27
DOI 10.18632/oncotarget.5408
PII 5408
PMID 26430873
PMC PMC4741497
MeSH Adult Aged Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Breast Neoplasms / metabolism* Breast Neoplasms / pathology Carcinoma, Ductal, Breast / metabolism* Carcinoma, Ductal, Breast / pathology Female Fluorescent Antibody Technique Humans Immunoblotting Immunohistochemistry Immunoprecipitation In Situ Nick-End Labeling Male Mice Mice, SCID Middle Aged Minichromosome Maintenance Complex Component 2 / biosynthesis* Polycomb Repressive Complex 1 / pharmacology RNA, Small Interfering Real-Time Polymerase Chain Reaction Recombinant Fusion Proteins / pharmacology Retroviridae Proteins, Oncogenic / pharmacology Transduction, Genetic Transfection Viral Envelope Proteins / pharmacology Xenograft Model Antitumor Assays
IF 5.168
Human and Animal Cells BALB/3T3 clone A31(RCB0005)