Related Experiment Video
Updated: Aug 9, 2026
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
04:12
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Differentiation genes: are they primary targets for human carcinogenesis?
K N Prasad1, A R Hovland, P Nahreini
1Center for Vitamins and Cancer Research, Department of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. kedar.prasad@uchsc.edu
Experimental Biology and Medicine (Maywood, N.J.)
|September 25, 2001
Summary
Cancer initiation may stem from the loss of differentiation genes, not oncogene mutations. This hypothesis suggests differentiation gene downregulation is the primary event in human carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Identifying primary targets in human carcinogenesis remains challenging.
- Mutated oncogenes or growth regulatory genes typically fail to immortalize or transform normal human epithelial cells, suggesting they are secondary events.
- Existing research suggests gene downregulation, specifically of differentiation genes, may be the primary event.
Purpose of the Study:
- To propose a novel hypothesis for human carcinogenesis.
- To identify potential primary targets in cancer development.
- To differentiate between tumor-initiating and tumor-promoting genes.
Main Methods:
- Review of experimental studies on molecular carcinogenesis.
- Analysis of gene function in cellular transformation and immortalization.
- Examination of differentiation induction in neuroblastoma (NB) cells using adenosine 3',5'-cyclic monophosphate (cAMP).
Main Results:
- Downregulation of a differentiation gene, termed a tumor-initiating gene, is hypothesized as the primary event in carcinogenesis.
- This downregulation can occur via mutation, activation of suppressor genes, or inactivation of tumor suppressor genes, leading to cell immortalization.
- Subsequent mutations in proto-oncogenes or growth regulatory genes in immortalized cells drive transformation, identifying them as tumor-promoting genes.
- Experiments with NB cells and cAMP support the hypothesis, showing that differentiation can be induced, but resistance indicates mutations or unresponsive regulatory genes.
- The hypothesis is applicable to various cancers including melanoma, glioma, and colon cancer.
Conclusions:
- The primary event in human carcinogenesis may be the downregulation of a differentiation gene (tumor-initiating gene).
- Cellular transformation occurs in subsequent steps involving tumor-promoting genes.
- This model provides a new framework for understanding carcinogenesis and identifying therapeutic targets.
More Related Videos
Related Concept Videos
02:21Cancers 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...
01:33Cancer-Critical Genes I: Proto-oncogenes
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...
01:33Cancer-Critical Genes I: Proto-oncogenes
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...
01:25Mutagenicity 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...