Ectopic Over-expression of Oncogene Pim-2 Induce Malignant Transformation of Nontumorous Human Liver Cell Line L02

Abstract

In order to prove that ectopic over-expression of Pim-2 could induce malignant transformation of human liver cell line L02, three groups of cells were set up including human liver cell line L02 (L02), L02 cells transfected with Pim-2 gene (L02/Pim-2) and L02 cells transfected with empty-vector (L02/Vector). Pim-2 expression levels were detected. The morphology, proliferation level, apoptosis rate and migration ability of the cells were detected respectively. Then the cells were subcutaneously inoculated into athymic mice and the microstructures of the neoplasm were observed. Compared with the controls, Pim-2 expression levels were significantly higher in L02/Pim-2 cells (P<0.05), and their morphology had obvious malignant changes. They also showed a significantly increased proliferation rate (P<0.05) and migration capacity (P<0.05), as well as a significantly decreased apoptosis rate (P<0.05). Only the athymic mice inoculated with L02/Pim-2 cells could generate neoplasm, and the morphology of the neoplasm coincided with that of the hepatoma. The results manifest that ectopic Pim-2 gene could be stably expressed in L02/Pim-2 cells. Both the morphological and biological changes of L02/Pim-2 cells demonstrate the trend of malignant transformation. L02/Pim-2 cells could generate hepatoma in athymic mice. In conclusion, Pim-2 could induce malignant transformation of human liver cell line L02.

Expression and function of PIM kinases in osteosarcoma

“…These results suggest that PIM kinases may affect OS metastasis. In agreement with this, previous studies have suggested a role for PIM kinases in cell motility and metastasis, for example, PIM1 was able to promote migration in leukemia and prostate cancer cells (48), PIM2 was shown to induce human liver cell malignant transformation and increase the migration rate (49), and PIM3 can promote ovarian cancer cell migration (50). In addition, absence of PIM kinases blocks the process of bone invasion induced by the 3-methylcholanthrene-induced sarcoma in vivo (51).…”

Inhibition of PIM2 in liver cancer decreases tumor cell proliferation in�vitro and in�vivo primarily through the modulation of cell cycle progression

“…In liver cancer, there is evidence to suggest that PIM2 expression is upregulated (28)(29)(30), e.g., by inhibiting apoptosis (29,30). As demonstrated in a previous study, upon the stable PIM2 overexpression in normal L02 liver cells, this otherwise non-tumorigenic cell line underwent malignant transformation to form tumor xenografts in a mouse model (31). These observations encouraged us to further explore PIM2 as a potential target for the treatment of liver cancer.…”

Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics

“…PIM2 has been shown to promote liver tumorigenesis through mediating cell survival and preventing liver cell apoptosis 50 . In the L02 human liver cell line, the stable ectopic expression of the PIM2 gene induces malignant transformations 51 , and knockdown of PIM2 in liver cancer results in potent anti-proliferative effects on cell growth G0/G1 cell-cycle blockade and the down-regulation of S phase and G2/M phase genes 52 .…”