| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
1)Effect of a differentiation inducer on characteristics of an ASCC cell line To investigate the origin of argyrophil small cell carcinoma (ASCC of the uterine cervix, we examined the influence of dibutyryl cyclic AMP (dB-cAMP), a known differentiation inducer, on characteristics of an ASCC cell line, TC-YIK, which has been demonstrated to be a useful in vitro experimental model of ASCC. In TC-YIK cells after treatment with dB-cAMP, specific antigenic markers of macrophage (CD14 and HLA-DR), and IFN-γ mRNA and protein were detected: Most of the cells were positive for α-naphtyl buyrate esterase stain, and some of the cells showed phagocytosis and adsorption of Micrococcus lysodeikticus. Furthermore, GM-CSF accelerated the proliferation of TC-YIK cells. These results indicate that dB-cAMP promotes a differentiation process to macrophage lineage in the ASCC cell line. In contrast, some of the cells showed stellate morphological changes, suggesting a neuronal differentiation after treatment with dB-cAMP. Thus, TC-YIK has been shown to differentiate both into macrophage lineage and neuronal cells, suggesting that ASCC may originate from undifferentiated stem cells.
2) Induction of apoptosis in TC-YIK cells by CDDP and effect of IFN-γ on the CDDP-induced apoptosis To investigate if IFN-γ can be used as an auxiliary drug of CDDP, a therapeutic drug for ASCC, we examined the effect and mechanism of IFN-γ on CDDP-induced apoptosis of TC-YIK. Apoptosis induction in TC-YIK cells by CDDP was increased after treatment with IFN-γ. The extent of Fas antigen expression on TC-YIK cells was in parallel with that of increase in the apoptosis of the cells. The increase of CDDP-induced apoptosis by IFN-γ was completely inhibited by a caspase inhibitor, Z-VADfmk. These results suggest that IFN-γ increases the CDDP-induced apoptosis through the increase in Fas antigen expression on TC-YIK cells, and that INF-γ could be used as an auxiliary therapeutic drug for ASCC.
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