Pim Family Kinases Enhance Tumor Growth of Prostate Cancer Cells

• Wei Wei Chen

  1Hollings Cancer Center and

• Daniel C. Chan

  3Division of Medical Oncology, University of Colorado Health Sciences Center, Denver, Colorado; and

• Carlton Donald

  2Department of Pathology, Medical University of South Carolina, Charleston, South Carolina;

• Michael B. Lilly

  4Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, Loma Linda, California

• Andrew S. Kraft

  1Hollings Cancer Center and

抄録

Recent analyses indicate that the expression of the Pim-1 protein kinase is elevated in biopsies of prostate tumors. To identify the mechanism by which the Pim kinases may affect the growth of prostate tumors, we expressed Pim-1, Pim-2, or a kinase-dead Pim-2 protein in human PC3 prostate cancer cells. On implantation of the transfectants in nude mice, the growth of the cells expressing Pim-1 or Pim-2 was significantly faster than the growth of the control cells transfected with the neomycin-resistant gene or the kinase-dead Pim-2 protein. When grown in medium, the doubling time of the Pim-1 and Pim-2 transfectants was faster (0.75 days) than that of the control cells (1.28 days). We, therefore, examined the ability of Pim to control the phosphorylation of proteins that regulate protein synthesis. On growth factor starvation or rapamycin treatment, the Pim-1 and Pim-2 transfectants maintained their ability to phosphorylate 4E-BP1 and S6 kinase, although this phosphorylation did not occur in the control-transfected PC3 cells. We have found that the cellular levels of c-Myc were elevated in the Pim-1 and Pim-2 transfectants under these conditions. The Pim-1 and Pim-2 transfectants have lower levels of serine/threonine protein phosphatase 2A (PP2A) activity and the α- and β-subunit B56γ of the PP2A phosphatase do not coimmunoprecipitate in these cells. Thus, the effects of Pim on PP2A activity may mediate the levels of c-Myc and the phosphorylation of proteins needed for increased protein synthesis. Both of these changes could have a significant impact on tumor growth.

収録刊行物

• Molecular Cancer Research

  Molecular Cancer Research 3 (8), 443-451, 2005-08-01

  American Association for Cancer Research (AACR)

キーワード

• Cancer Research
• Oncology
• Molecular Biology

詳細情報

• CRID: 1363670318213085568
• NII論文ID: 30018581362
• DOI: 10.1158/1541-7786.mcr-05-0007
• ISSN: 15573125
• ISSN: 15417786
• Web Site: https://aacrjournals.org/mcr/article-pdf/3/8/443/3139033/443-451.pdf
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