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p53遺伝子導入により誘導されるアポトーシスにはNF-kB活性の抑制が関与している：邵　江華, 藤原俊義, 片岡正文, 西崎正彦, 門脇嘉彦, 深澤拓也, 日伝晶夫, 田中紀章（岡山大・医・一外）

Inhibition of NF-kB activity is involved in apoptosis induced by wild-type p53 gene transfer: Jianghua SHAO, Toshiyoshi FUJIWARA, Masafumi KATAOKA, Masahiko NISHIZAKI, Yoshihiko KADOWAKI, Takuya FUKAZAWA, Akio HIZUTA, Noriaki TANAKA (1st Dept. Surg., Okayama Univ. Med. Sch.)

The p53 tumor suppressor gene is involved in multiple central cellular processes, one of the most important role is apoptosis. However, the exact mechanism of p53-mediated apoptosis is not clear. Recently, activation of the transcriptional factor nuclear factor-kB (NF-kB) has been shown to induce expression of genes that mediate anti-apoptosis. We investigated the effect of recombinant adenovirus expressing the wild-type p53 gene (Ad-p53) on NF-kB activity in a human colon cancer cell line DLD-1 with mutant form of p53. Infection with Ad-p53 resulted in a rapid cell death, indicative of apoptosis by FACS. Western blot analysis demonstrated that Ad-p53 dramatically suppressed NF-kB protein expression in nuclear extract as early as 8 hours after infection. Immunohistochemical staining also showed that nuclear accumulation of NF-kB protein occurred in cells treated with anti-cancer drug, adriamycin, whereas Ad-p53 infection blocked this activation of NF-kB. Thus, adenovirus-mediated p53 gene transfer may induce apoptosis through down-regulation of NF-kB in both concentration- and time-dependent manner. These results suggest that inhibition of NF-kB is a plausible mechanism for p53-mediated apoptosis.