Pim family kinases enhance tumor growth of prostate cancer cells

Wei Wei Chen, Daniel C. Chan, Carlton Donald, Michael B. Lilly, Andrew Kraft

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

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 56 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.

Original languageEnglish (US)
Pages (from-to)443-451
Number of pages9
JournalMolecular Cancer Research
Volume3
Issue number8
DOIs
StatePublished - Aug 2005
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Protein Phosphatase 2
Growth
Neoplasms
Phosphorylation
Proteins
Proto-Oncogene Proteins c-pim-1
Prostate
Proto-Oncogene Proteins c-myc
Neomycin
Sirolimus
Threonine
Starvation
Phosphoric Monoester Hydrolases
Nude Mice
Protein Kinases
Serine
proto-oncogene proteins pim
Intercellular Signaling Peptides and Proteins
Phosphotransferases

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Pim family kinases enhance tumor growth of prostate cancer cells. / Chen, Wei Wei; Chan, Daniel C.; Donald, Carlton; Lilly, Michael B.; Kraft, Andrew.

In: Molecular Cancer Research, Vol. 3, No. 8, 08.2005, p. 443-451.

Research output: Contribution to journalArticle

Chen, Wei Wei ; Chan, Daniel C. ; Donald, Carlton ; Lilly, Michael B. ; Kraft, Andrew. / Pim family kinases enhance tumor growth of prostate cancer cells. In: Molecular Cancer Research. 2005 ; Vol. 3, No. 8. pp. 443-451.
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