Development of Diagnosis and Treatment of Malignant Diseases Based on the Expression of DNaseγ

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RT-PCR revealed the expression of mRNA for GnRH and its receptor in human epithelial ovarian cancer cell lines (HTOA, OV-1063 and OVCAR-3) and human endometrial cancer cell lines (HEC-1 and HHUA). Furthermore, the expression of mRNA of DNaseγ and CAD (caspase 3-activated DNase) was also detected by RT-PCR in these cell lines. The GnRH agonist, buserelin, and the GnRH antagonist, cetrorelix, increased the incidence of apoptosis in cultured HTOA cells as determined by TUNEL staining. The treatment with both analogs suppressed the growth of xenografts of HTOA cell line in nude mice to the same extent. In cultured HTOA cells, the both GnRH analogs suppressed EGF-induced tyrosine phosphorylation of EGF receptor and blocked cell cycle progression in G0/G1 phase. These findings lead us to suggest that the antineoplastic actions of both GnRH analogs might be based on apoptosis induced by the activation of DNase, suppression of EGF-induced signaling pathway or cell cycle arrest at G1. On the other hand, in the five cell lines described above, the expression of DNaseγ protein could not be detected in these cell lines by Western blotting using anti-DNaseγ polyclonal and monoclonal antibodies generated by us previously. Then a remarkably specific anti-DNaseγ monoclonal antibody was newly generated. This antibody has been shown to be useful for Western blotting and ELISA.