title: Knockdown of Pim-3 suppresses the tumorigenicity of glioblastoma by regulating cell cycle and apoptosis.
abstract: Products of the Pim (the proviral integration site for the Moloney murine leukemia virus) family of proto&mdash;oncogenes possess serine/threonine kinase activity and belong to the Ca2+/calmodulin&mdash;dependent protein kinase group. Pim&mdash;3, a member of the Pim family is closely linked to the development of a variety of tumors. However, the role of Pim&mdash;3 in human glioblastoma remains unknown. In this study, we elucidated the role of Pim&mdash;3 in the growth and apoptosis of glioblastoma cells. Western blotting was used for determination of protein levels, and shRNA was used for Pim&mdash;3 knockdown. The MTT assay was used to evaluate cell proliferation and flow cytometry was used to determine cell cycle status and the number of apoptotic cells. A mouse xenograft model was established by injecting nude mice with Pim&mdash;3&mdash;depleted glioblastoma cells in order to determine tumor growth in vivo. We demonstrated that Pim&mdash;3 was highly expressed in human glioblastoma cell lines. We also found that knockdown of Pim&mdash;3 by specific shRNA slowed decreased proliferation, induced cell cycle arrest in the G0/G1 phase, and increased apoptosis in glioblastoma cells. Pim&mdash;3 knockdown potently inhibited the growth of subcutaneously implanted glioblastoma cells in vivo. We further revealed that Pim&mdash;3 knockdown induced growth inhibition by reducing the levels of the anti&mdash;apoptotic protein Bcl&mdash;xl and cell cycle regulatory proteins, including cyclin D1 and Cdc25C, and increasing the levels of the pro&mdash;apoptotic protein Bax.
authors: The Second Affiliated Hospital of Xi&apos;an Jiao Tong University Department of Neurosurgery Xi&apos;an China.
authors: J
authors: J
authors: Quan
authors: The Second Affiliated Hospital of Xi&apos;an Jiao Tong University Department of Neurosurgery Xi&apos;an China.
authors: L
authors: L
authors: Zhou
authors: The Second Affiliated Hospital of Xi&apos;an Jiao Tong University Department of Neurosurgery Xi&apos;an China lxgang_lxg&commat;163.com.
authors: J
authors: J
authors: Qu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D063646:Carcinogenesis / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D016543:Central Nervous System Neoplasms / Q000473:pathology* / Q000503:physiopathology; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology; D064593:Heterografts; D006801:Humans; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019938:Cyclin D1; C499249:PIM3 protein, human; D017346:Protein Serine-Threonine Kinases; D020687:cdc25 Phosphatases