title: p73alpha regulates the sensitivity of bone marrow mesenchymal stem cells to DNA damage agents.
abstract: Human bone marrow mesenchymal stem cells (MSCs) are important cell population located in bone marrow that are thought to have multiple functions in cell transplantation and gene therapy. Although in vitro experiments have demonstrated that hMSCs are resistant to apoptosis induction by DNA damage agents such as chemotherapeutic substances used in bone marrow transplantation, the molecular mechanism underlying remains unclear. p73 is highly similar to p53 and plays crucial roles in regulating DNA damage-induced apoptosis pathways. In this study, we investigated the role of p73 alpha in response to chemotherapeutic substances in cultured human bone marrow MSCs. Cellular chemosensitivity and DNA damage-induced apoptotic cell death were examined in the hMSCs with exogenously over-expressed p73 alpha. Our results showed that the expression of retrovirus-driven human p73 alpha could be successfully induced in hMSCs, the over-expression of ectopic p73 alpha resulted in a significant increase of cellular sensitivity to cisplatin. The increase of cellular apoptosis was attributed to enhanced chemosensitivity in p73 alpha infected cells. Moreover, immunoblot analysis indicated that the co-activation of pro-apoptotic factors Bax and p21 were observed in the p73 alpha infected cells after cisplatin treatment. In conclusion, our findings suggested that p73 alpha is an important determinant of cellular chemosensitivity in human bone marrow MSCs.
authors.affiliation: Institute of Basic Medical Sciences and School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, 5# Dongdansantiao, Beijing 100005, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: James Q
authors.initials: JQ
authors.lastname: Yin
authors.forename: Robert Chunhua
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D020014:K562 Cells; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D012190:Retroviridae / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D002945:Cisplatin