ゾウにおけるがん抵抗性の潜在的メカニズムとヒトにおけるDNA損傷に対する比較的な細胞反応
Lisa M Abegglen1, Aleah F Caulin2, Ashley Chan1
1Departments of Pediatrics (Hematology/Oncology) and Oncological Sciences, University of Utah School of Medicine, Salt Lake City.
JAMA
|October 9, 2015
まとめ
ゾウは TP53 遺伝子の複製により 驚くべき抗がん性を示しています ゾウの細胞はヒトの細胞と比較して DNAの損傷に対する アポプトシス反応が強くなり 癌抑制の進化の洞察を与えてくれます
科学分野:
- 進化 的 な 医学
- 比較腫瘍学
- ゲノミクス
背景:
- 進化医学はヒトの生理学や 癌の生物学を含む病気の洞察力を提供します
- ゾウは 大きさと長寿にもかかわらず 癌に耐性を示し 独特の細胞メカニズムの研究を促しています
研究 の 目的:
- ゾウの抗癌メカニズムを特定するために
- ゾウ,健康な人間,リ・フラウメニ症候群 (LFS) 患者におけるDNA損傷に対する細胞反応を比較する.
主な方法:
- 644頭のゾウを含む36種の哺乳類の解剖データを分析し,がんに対する耐性を評価した.
- アフリカやアジアゾウのゲノムを解析し 癌に対する耐性遺伝子を特定しました
- ゾウ,ヒトの対照群,およびLFS患者からの外周血液リンパ球を電離放射線とドクソルビシンにさらし,DNA損傷反応とアポトーシスを比較した.
主要な成果:
- 癌による死亡率は,哺乳類の体積や寿命と相関せず,象の死亡率は人間より低い (4. 81%) であった.
- アフリカのゾウは TP53 遺伝子の少なくとも20個のコピーを持っているが,人間には2つのコピーがある.
- ゾウのリンパ球はヒトのリンパ球と比較して,p53媒介によるアポトーシスの割合が著しく高かった.
結論:
- ゾウの癌率の低下は TP53遺伝子の複製と関連している可能性があります.
- DNA損傷後のゾウの細胞における 強化されたアポプトシス反応は 強力な癌抑制メカニズムを示唆しています
- これらの発見は 癌抑制の研究における 進化論に基づく戦略の道を開くかもしれません
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