The significance of PAI-2 expression in human tumors is unclear. The prognostic significance of a high PAI-2 expression in various tumors is controversial. In vitro, PAI-2 has been found to protect tumor cells from TNFot-induced apoptosis. In this study, a plasmid pCI-J7 was constructed by inserting the entire coding region of PAI-2 into the EcoRl site of the pCI-neo expression vector. The same vector was also used for the construction and expression of an inactive PAI-2, which contained an alanine for arginine substitution at the PI residue at position 380 (pCI-J7ili3go). These two plasmids were transfected into the rat prostate cancer cell line MATLyLu, and inoculated subcutaneously into Copenhagen rats. Primary tumor and metastatic lesions were studied in animals sacrificed at day 14. Using the TUNEL method, the primary tumors showed decreased apoptosis in tumor cells expressing wild-type PAI-2 (0.53 ±0.50%) compared to cells expressing mutant PAI-2 (5.91+4.15%) (P<0.005), or to the non-transfected cells (2.38 ± 2.45%) (P <0.05). Cells expressing mutant PAI-2 showed more apoptosis than the nontransfected cells (P<0.05). There were no visible lung métastases in the wild-type PAI-2 group, whereas 5-10 lesions (<lmm2) were found in 2 of 6 mutant PAI-2 group, and 2-3 lesions (2-4 mm2) in 2 of 6 non-transfected group. Taken together, these data demonstrated that PAI-2 can inhibit apoptosis and metastasis in vivo.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - Dec 1 2000|
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