PTENの全身的上昇は,腫瘍を抑制する代謝状態を誘発する
Isabel Garcia-Cao1, Min Sup Song, Robin M Hobbs
1Cancer Genetics Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cell
|March 10, 2012
まとめ
ネズミのPTEN (ホモログのフォスファタゼとテンシン) レベルを上昇させると,がんのリスクが低下し,健康な代謝を促進します. この発見は,PTENの上昇が癌の予防と治療のための潜在的な戦略であることを示唆しています.
科学分野:
- 腫瘍学 腫瘍学
- メタボリック研究.
- 遺伝学 遺伝学とは
背景:
- PTEN (フォスファタゼとテンシンホモログ) 機能の喪失は,がんの発症と進行に関連しています.
- PTENレベルを回復または増加させることは,がんの予防と治療のための新しいアプローチを提供することができます.
研究 の 目的:
- 増加したPTEN発現が身体の健康,代謝,がんに対する抵抗力に及ぼす影響を調査する.
- PTENが細胞代謝と腫瘍性変異に影響を与える根本的なメカニズムを探求する.
主な方法:
- バクテリア人工染色体 (BAC) 媒介型トランスジェネシスを使用して,さまざまなレベルのPTEN発現を持つトランスジェニックマウスラインを生成しました.
- 体のサイズ,代謝,エネルギー消費,体脂肪の蓄積を含む生理学的パラメータを分析した.
- 評価された細胞代謝プロフィール,グルコースとグルタミンインの摂取量,ミトコンドリアの活性,および腫瘍原性変異に対する抵抗を含む.
- PTENの代謝効果を媒介するPI3K依存およびPI3K独立経路の役割を調査した.
主要な成果:
- 生存可能な"スーパー-PTEN"マウスは,細胞数が減少したため,体のサイズが小さくなりましたが,正常な細胞サイズを維持しました.
- PTENの上昇は,より健康的な代謝プロファイルにつながり,エネルギー消費が増加し,体脂肪が減少しました.
- PTENが増加した細胞は,グルコースとグルタミン吸収の減少,ミトコンドリアの酸化性リン酸化の強化,および腫瘍性変異に対する抵抗を示した.
- PTENの上昇はグルタミノリシスとウォーバーグ効果を抑制し,腫瘍細胞における主要な代謝変化である.
結論:
- 生物のレベルでのPTENの上昇は,腫瘍性変異に対する抵抗性を与え,代謝的に健康な状態を促進します.
- PTENは,潜在的にPI3K依存およびPI3K独立経路を通じて,グルコースとグルタミン代謝に影響を与える代謝スイッチを調節する.
- これらの発見は,細胞代謝を調節することにより,がんの予防と治療のための有望なターゲットとしてPTENを強調しています.
関連する概念動画
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...