IMUP-1 and IMUP-2 genes are up-regulated in human ovarian epithelial tumors

Abstract

BACKGROUND: Normal cells lose their ability to divide after a finite number of cell divisions. Under the influence of Simian virus 40 (SV 40) large T-antigen, which interacts with the cell cycle regulators p53 and pRb, cells enter a phase of an extended pre-immortalized cells. Immortalization-up-regulated protein 1 (IMUP-1) and immortalization-up-regulated protein 2 (IMUP-2) genes have been recently cloned and are known to be involved in SV40-mediated immortalization. However, the roles of IMUP-1 and IMUP-2 are not known in human ovarian epithelial tumors. PATIENTS AND METHODS: This study was performed to determine mRNA expression and intracellular localization of the IMUP-1 and IMUP-2 in ovarian epithelial tumors by RT-PCR and immunohistochemical staining using human IMUP-1 and IMUP-2 monoclonal antibodies. RESULTS: IMUP-1 (4.0-fold) and IMUP-2 (2.4-fold) mRNA expression in ovarian epithelial tumors were significantly higher than in normal ovarian tissues (p < 0.05). The mRNAs of IMUP-1 and IMUP-2 in the ovarian cancer cell lines were about 4.9- and 2.9-fold compared to the normal ovarian cell line, respectively. The subcellular expression of these two proteins in immunohistochemical stains was detected mainly in the nucleus of tumor cells, whereas adjacent normal ovarian stromal cells were faintly or negatively stained with these proteins. However, the staining intensity of IMUP-1 and IMUP-2 in ovarian epithelial tumors were not different between histological types or grades. CONCLUSION: These results showed the up-regulation of IMUP-1 and IMUP-2 in human ovarian epithelial tumors and suggested that the altered mRNA level of these molecules is possibly associated with ovarian tumorigenesis.