短い機能不全テロメアは,INK4a (デルタ2/3) がんに罹患しやすいマウスの腫瘍形成を阻害する
R A Greenberg1, L Chin, A Femino
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cell
|May 25, 1999
まとめ
テロメア縮小は,テロメラーゼRNA (mTR) とINK4aが欠けているマウスにおける腫瘍形成を阻害する. mTRを復元することで,再確立されたがん促進の可能性を回復させ,テロメアの維持を強調します.
科学分野:
- がん生物学 がん生物学
- 遺伝学 遺伝学とは
- 細胞老化 細胞の老化
背景:
- テロメア長さの維持は,がん細胞の生存と増殖に不可欠です.
- テロメア機能不全は,腫瘍発生の障壁として作用する可能性があります.
- テロメア生物学と腫瘍抑制遺伝子の相互作用は複雑である.
研究 の 目的:
- テロメア機能障害がマウスモデルで腫瘍形成に及ぼす影響を調査する.
- 腫瘍発現におけるテロメラーゼRNA (mTR) とINK4aの役割を評価する.
- テロメラーゼの活性化が,極めて短いテロメアを持つ細胞における悪性変異に必要かどうかを判断する.
主な方法:
- テロメラーゼRNA (mTR) とINK4a腫瘍抑制遺伝子の両方を欠くマウスの次世代を生成しました.
- 生体内での腫瘍形成と,世代を超えて,体内での腫瘍発生の可能性を評価した.
- 腫瘍発生の可能性の回復を評価するために,欠陥細胞にmTRを再導入した.
主要な成果:
- テロメラーゼ欠乏性マウスの後期世代は,腫瘍形成と腫瘍発生の可能性が著しく低下したことを示した.
- 重度のテロメア短縮と機能障害は,これらの後期世代で観察されました.
- mTRの再導入は,極めて短いテロメアを持つ細胞における腫瘍学的可能性を回復させた.
結論:
- テロメア機能の喪失は,がんに罹患しやすいモデルでも,DNA損傷反応が整っている場合でも,腫瘍形成を阻害しますが,完全に防ぐわけではありません.
- テロメラーゼの活性化は,悪性変異を促進するために,極めて短いテロメアと協力します.
- テロメア維持は,がんの発達と進行における重要な要因です.
さらに関連する動画
06:09Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
8.6K
10:49A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers
Published on: September 26, 2019
5.2K
関連する概念動画
02:41Telomeres and Telomerase
23.1K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.1K
02:15Replicative Cell Senescence
3.5K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.5K
02:23Abnormal Proliferation
4.0K
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...
4.0K
01:12Loss of Tumor Suppressor Gene Functions
4.9K
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...
4.9K
02:43Mouse Models of Cancer Study
4.7K
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
4.7K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
8.3K
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...
8.3K