| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
The larynx is an androgen target as a secondary sexual organ ; laryngeal epithelial cells have an affinity for androgen in the cell nucleus. Cancer of the larynx is the fourteenth most common incident cancer throughout the world. An estimated 190, 000 new cases were diagnosed worldwide (WHO, 1997), accounting for 1.8% of all new cancers. Men comprise 85% of the worldwide incidence of laryngeal cancer.
In this study, the laryngeal carcinoma cell line (HEp-2) was used to examine the relation of the laryngeal cancer to androgen. Two days after the treatment of 10^<-6>M testosterone propionate (Tp), the cell numbers increased, but thereafter decreased and greater than 95% of the cells died within three days, bearing no relation to cell-to-cell contact inhibition. As well as androgen, estrogen is also efficient for inducing HEp-2 cell death, however, its required concentration is one order higher (>10^<-5>M) in comparison with the tp's, but progesterone, corticosterone and cortisone are not.
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The RT-PCR products suggested that the HEp-2 cell has a faculty for transcripting the androgen receptor (AR), aromatase and estrogen receptor (ER)- β genes, but not the 5 α -reductase-I, -II, ER- α and 17 β-hydroxyrase I〜III genes. The anti-sense oligo-nucleotide transfection study suggested that this cell death needs the newly transcribing AR gene. The Tp triggers a distinct induction of SRC but the barely detectable P53 mRNA, despite the fact of marked augmentation of the P53 protein level (Tp : Control = 1242.1 : 96.6 pg/mg.p). There is no clear distinction upon transcription of the AR, HPV18-E6, -E7 and CBP genes between the Tp-treated and non-treated cells, while there is no transcription of the Rb, caspase-3, and HPV18-E2 and HPV16-E6 genes.
Taken together, these results imply that androgen may interfere with the physiology of laryngeal cancer cells, depending upon the new transcription of the AR gene and some metabolism of androgen to estrogen under the constant presence of durable p53 proteins and HPV18 in some cases. Less
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