Mutational analysis of AKT1, AKT2 and AKT3 genes in common human carcinomas

Young Hwa Soung1, Jong Woo Lee, Suk Woo Nam

  • 1Department of Pathology, College of Medicine, Catholic University of Korea, Banpo-Dong, Socho-Gu, Seoul, Korea.

Oncology
|October 19, 2006
PubMed
Abstract

Insights

AKT gene mutations are uncommon in common human cancers. This study found AKT2 mutations in a small percentage of stomach and lung carcinomas, suggesting a role in cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alterations in AKT proteins are implicated in cancer development.
  • Investigating AKT mutations in common human carcinomas is crucial for understanding cancer pathogenesis.

Purpose of the Study:

  • To determine if common human carcinomas harbor AKT mutations.
  • To assess the role of AKT mutations in cancer development.

Main Methods:

  • Mutational analysis of AKT1-AKT3 kinase domains using single-strand conformation polymorphism assay.
  • Analysis performed on 294 carcinoma tissues from stomach, lung, colon, and breast.

Main Results:

  • Three somatic mutations were detected in AKT2; no mutations were found in AKT1 or AKT3.
  • AKT2 mutations occurred in 2.0% of gastric and 2.5% of lung carcinomas.
  • One lung adenocarcinoma with an AKT2 missense mutation also had an EGFR mutation.

Conclusions:

  • Somatic mutations in the AKT2 kinase domain are rare in common human cancers.
  • AKT2 mutations may contribute to the development of certain human cancers via altered signaling pathways.

Related Concept Videos

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...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
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...