| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
Roles of androgens in maintaining the hemostasis of androgen-dependent tissues by controlling cell proriferation as well as cell death or apoptosis have been well documented.
In the present study, we undertook the following experiments to survey the physiological role and the molecular mechanism of apoptosis in androgen-dependent tissues. These experiments were performed by using male accessory sex organs of rats and the androgen-dependent Shionogi Carcinoma 115 (SC115) as experimental model systems.
(1) Gene expression associates with apoptosis : A number of genes responding to the androgen withdrawal has been identified as candidates playing potential roles during the process of apoptosis. Since a potential role of c-myc induction has been recently suggested, we focused our interest on the expression of Max, which specifically hetero-dimerise with c-Myc and exhibits the biological activity. We have isolated for the first time the rat Max cDNA and demonstrated the castration-induced exp
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ression of the 2 kb transcript in male accessory sex organs of rats (Izawa, Biochim Biophys Acta 1216,412,1993). We have also identified an alternative form of rat TRPM-2, one of molecular markers of apoptosis in many types of cells (Izawa, submitted for publication).
(2) New assay method for genomic DNA fragmentation : Using genomic DNA as probe, we have developed a new and sensitive Southern hybridization method to assay the genomic DNA fragmented into a nucleosome unit, a distinct molecular marker of apoptosis. Using this assay, we could easily examine the cells undergoing apoptosis.
(3) Cloning and selection of CS115-derived cells exhibiting androgen-dependent apoptosis : We have succeeded in isolation 3groups of SC115-derived cell clones ; cells, dependent on serum and androgen, dependent on androgen alone and independent on serum and androgen (Izawa, submitted for publication).
Toward understanding the role of apoptosis in androgen-dependent tissues, we could obtain useful probes and excellent experimental model systems in the present study. Less
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