Related Experiment Video

Updated: Aug 7, 2026

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice

Mei-Ling Chen1, Pei-Zhang Xu, Xiao-ding Peng

  • 1Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois 60607, USA.

Genes & Development
|June 17, 2006
PubMed

Insights

Tumor suppressor PTEN inactivation leads to Akt hyperactivation. Akt1 deficiency significantly inhibits tumor development in Pten-deficient mice, impacting various cancers and offering therapeutic implications.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The tumor suppressor PTEN is frequently inactivated in human cancers, leading to hyperactivation of its downstream effector, Akt.
  • The role of diminished Akt activity in inhibiting tumorigenesis initiated by Pten deficiency remains unclear.

Purpose of the Study:

  • To investigate whether Akt1 deficiency is sufficient to inhibit tumor development in the context of Pten deficiency.
  • To explore the impact of Akt1 deficiency on specific cancer types associated with PTEN mutations.

Main Methods:

  • Utilizing a genetically modified mouse model (Pten+/- mice) with varying Akt1 deficiency levels.
  • Analyzing the effect of Akt1 haplodeficiency and deficiency on tumor development, including prostate intraepithelial neoplasia (PIN) and endometrial carcinoma.

Main Results:

  • Akt1 deficiency dramatically inhibited tumor development in Pten+/- mice.
  • Akt1 deficiency significantly affected endometrium and prostate neoplasia, thyroid and adrenal medulla tumors, and intestinal polyps.
  • Even haplodeficiency of Akt1 markedly attenuated the development of high-grade PIN and endometrial carcinoma.

Conclusions:

  • Diminished Akt activity, specifically Akt1 deficiency, is sufficient to inhibit tumorigenesis initiated by Pten deficiency.
  • Targeting Akt1 could be a promising therapeutic strategy for PTEN-mutated cancers.
  • These findings have significant implications for developing novel cancer therapies.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Abnormal Proliferation02:23

Abnormal 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...
mTOR Signaling and Cancer Progression03:03

mTOR 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...
Loss of Tumor Suppressor Gene Functions01:12

Loss 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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...