Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis

  • Authors:
    • Bin Liu
    • Zhen Wang
    • Hong-Yu Li
    • Bo Zhang
    • Bo Ping
    • Ying-Yi Li
  • View Affiliations

  • Published online on: April 25, 2014     https://doi.org/10.3892/or.2014.3158
  • Pages: 2625-2634
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Abstract

Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in malignant lesions, but not in normal pancreatic tissues. To assess the role of Pim-3 in human pancreatic carcinogenesis in vivo and to determine the underlying Pim-3 signaling regulatory mechanisms, we established MiaPaca-2 cells overexpressing wild-type Pim-3 or Pim-3 kinase dead mutants (K69M-Pim-3) as well as PCI55 cells stably expressing Pim-3 shRNA or scrambled shRNA in a tetracycline-inducible manner. In addition, we conducted studies utilizing a nude mouse tumor xenograft model. Our results demonstrated that cells stably overexpressing wild-type Pim-3 exhibited functionally enhanced phosphorylation of Bad at Ser112 and increased proliferation. In contrast, the stable inactivation of Pim-3 by K69M-Pim-3 or silencing of Pim-3 expression by Pim-3 shRNA resulted in functionally decreased phosphorylation of Bad at Ser112 and higher apoptotic cells. Following subcutaneous injection of these stable cell lines, nude mice injected with Pim-3 overexpressing cells developed 100% subcutaneous tumors, together with increased PCNA-positive cells and enhanced intratumoral CD31-positive vascular areas. On the other hand, intratumoral neovascularization and tumor cell proliferation was attenuated in mice injected with Pim-3 kinase inactive cells, eventually reducing tumorigenicity in these mice to 46.6%. Moreover, Pim-3 overexpression upregulated the intratumoral levels of pSTAT3Try705, pSurvivinThr34, HGF, EGF, FGF-2 and VEGF, while the increases were markedly diminished on Pim-3 kinase inactivation. Collectively, the Pim-3 kinase emerges as being involved in accelerating human pancreatic cancer development and in promoting tumor neovascularization and subsequent tumor growth. Targeting Pim-3 may play a dual role in halting tumor progression, by promoting tumor cell death and blocking angiogenesis.

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Copy and paste a formatted citation
APA
Liu, B., Wang, Z., Li, H., Zhang, B., Ping, B., & Li, Y. (2014). Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis. Oncology Reports, 31, 2625-2634. https://doi.org/10.3892/or.2014.3158
MLA
Liu, B., Wang, Z., Li, H., Zhang, B., Ping, B., Li, Y."Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis". Oncology Reports 31.6 (2014): 2625-2634.
Chicago
Liu, B., Wang, Z., Li, H., Zhang, B., Ping, B., Li, Y."Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis". Oncology Reports 31, no. 6 (2014): 2625-2634. https://doi.org/10.3892/or.2014.3158