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Article

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 / Copyright

    Affiliations: Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China, Department of Gastroenterology, Shenyang General Hospital, Shenyang, Liaoning, P.R. China, Department of Pancreas and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China, Department of Pathology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China
  • Pages: 2625-2634
    |
    Published online on: April 25, 2014
       https://doi.org/10.3892/or.2014.3158
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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
Spandidos Publications style
Liu B, Wang Z, Li H, Zhang B, Ping B and Li Y: Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis. Oncol Rep 31: 2625-2634, 2014.
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
Copy and paste a formatted citation
x
Spandidos Publications style
Liu B, Wang Z, Li H, Zhang B, Ping B and Li Y: Pim-3 promotes human pancreatic cancer growth by regulating tumor vasculogenesis. Oncol Rep 31: 2625-2634, 2014.
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
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