Zheng HC, Tsuneyama K, Takahashi H, Miwa S, Sugiyama T, Popivanova BK et al.. Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression. J Cancer Res Clin Oncol 134: 481-488

Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan.
Journal of Cancer Research and Clinical Oncology (Impact Factor: 3.08). 04/2008; 134(4):481-8. DOI: 10.1007/s00432-007-0310-1
Source: PubMed


Pim-3, a member of the proto-oncogene Pim family with serine/threonine kinase activity was aberrantly expressed in cancerous lesions of endoderm-derived organs such as liver, pancreas, and colon. The aim of this study was to clarify the role of Pim-3 expression in the tumorigenesis and the development of gastric carcinomas.
Pim-3 expression was immunohistochemically examined on the tissue microarrays containing primary (n = 285) and metastastic (n = 37) sites of gastric carcinomas, in comparison with adenoma (n = 48) and non-cancerous mucosa (n = 84). It was also compared with the clinicopathological parameters of gastric carcinomas.
Pim-3 expression was enhanced in adenoma (64.6%) and metastasis sites of gastric carcinoma (73.0%), to a lesser degree in primary sites of gastric carcinoma (39.3%) when compared to non-cancerous mucosa (13.1%, p < 0.0001). Pim-3 expression levels were higher in intestinal-type than diffuse-type gastric carcinoma (p = 0.018). Pim-3 expression was closely correlated with sex (p = 0.047), lymphatic (p = 0.019) and venous invasion (p = 0.014). Pim-3 expression was correlated significantly with vascular endothelial growth factor (VEGF, p = 0.009) and extracellular matrix metalloproteinase inducer (EMMPRIN, p = 0.032), both of which are presumed to be involved in neovascularization, a crucial step for metastasis. On the contrary, phosphatase and tensin homology deleted from human chromosome 10 (Pten) negative gastric carcinomas exhibited higher Pim-3 expression than Pten positive ones (p = 0.042). There was no relationship between Pim-3 expression and MVD in gastric carcinomas (p = 0.715). Furthermore, patients with Pim-3 positive gastric cancer, showed a lower cumulative survival rate than those with Pim-3 negative gastric cancer (p = 0.014) and Pim-3 positive was also identified as an independent prognostic factor for gastric carcinoma patients (p = 0.006).
Aberrant Pim-3 expression was involved in gastric adenoma-adenocarcinoma sequence and subsequent invasion and metastasis process in gastric cancer. Moreover, Pim-3 may be employed to predict the prognosis of gastric cancer patients. Distinct Pim-3 expression underlies the molecular mechanisms for the differentiation of intestinal-type and diffuse-type carcinomas.

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    • "These data suggested that disease stage-averaged mRNA expressions for genes PIK3C3, PIM3, and PTEN could be used for breast cancer diagnosis but not for the other types of cancer. Since previous studies have shown upregulation of PIM3 or downregulation of PTEN in various types of cancer [33–36], the disease stage-averaged method may have neglected important information about the mRNA expressions of the three genes. "
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    ABSTRACT: Poor prognosis for late-stage, high-grade, and recurrent cancers has been motivating cancer researchers to search for more efficient biomarkers to identify the onset of cancer. Recent advances in constructing and dynamically analyzing biomolecular networks for different types of cancer have provided a promising novel strategy to detect tumorigenesis and metastasis. The observation of different biomolecular networks associated with normal and cancerous states led us to hypothesize that correlations for gene expressions could serve as valid indicators of early cancer development. In this pilot study, we tested our hypothesis by examining whether the mRNA expressions of three randomly selected cancer-related genes PIK3C3, PIM3, and PTEN were correlated during cancer progression and the correlation coefficients could be used for cancer diagnosis. Strong correlations (0.68 ≤ r ≤ 1.0) were observed between PIK3C3 and PIM3 in breast cancer, between PIK3C3 and PTEN in breast and ovary cancers, and between PIM3 and PTEN in breast, kidney, liver, and thyroid cancers during disease progression, implicating that the correlations for cancer network gene expressions could serve as a supplement to current clinical biomarkers, such as cancer antigens, for early cancer diagnosis.
    04/2014; 2014:253804. DOI:10.1155/2014/253804
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    • "Pim kinase expression has been associated with poor outcome in several different tumor types [45-58] and chemoresistance have been seen in tumor cells overexpressing the Pim kinases [59-62]. This has inspired efforts to inhibit the Pim kinases as a cancer treatment. "
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    ABSTRACT: The Pim kinases are weak oncogenes. However, when co-expressed with a strong oncogene, such as c-Myc, Pim kinases potentiate the oncogenic effect resulting in an acceleration of tumorigenesis. In this study we show that the least studied Pim kinase, Pim-3, is encoded by a gene directly regulated by c-Myc via binding to one of the conserved E-boxes within the Pim3 gene. Accordingly, lymphomas arising in Myc-transgenic mice and Burkitt lymphoma cell lines exhibit elevated levels of Pim-3. Interestingly, inhibition of Pim kinases by a novel pan-Pim kinase inhibitor, Pimi, in Myc-induced lymphoma results in cell death that appears independent of caspases. The data indicate that Pim kinase inhibition could be a viable treatment strategy in certain human lymphomas that rely on Pim-3 kinase expression.
    Oncotarget 06/2011; 2(6):448-60. DOI:10.18632/oncotarget.283 · 6.36 Impact Factor
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    ABSTRACT: AIM: To investigate the role of Pim-3 aberrant expression in the development of gastric carcinoma. METHODS: Semi-quantitative RT-PCR method and immunohistochemistry method were used to detect the expression of Pim-3 in 40 gastric carcinoma tissues and 20 adjacent normal tis- sues. We also compared relationship between Pim-3 expression and the clinicopathological parameters of gastric carcinoma. RESULTS: Pim-3 mRNA expression was en- hanced in gastric carcinoma compared with non- cancerous mucosa (0.287 ± 0.058 vs 0.053 ± 0.055, P < 0.001). Protein expression of Pim-3 was significantly higher in moderately differentiated adenocarcinoma tissue than in poorly differenti- ated adenocarcinoma tissue. Pim-3 expression was closely correlated with lymphatic metastasis and venous invasion (r = 0.385, 0.412, P = 0.014, 0.008).
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