Carcinogenesis - Mechanism of action. Proto-Oncogenes vs Oncogenes, tumor suppressor gene P53
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3 سال پیش
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Carcinogenesis is a complex process,
Carcinogenesis is a complex process, in which, normal cells are transformed into cancer cells.
Carcinogenesis would not happen without mutation.
Mutation is an alteration in the genome of an organism.
A single mutation is not enough, to develop cancer.
It requires, several mutations in the genome.
There are two main sources to get mutation.
First. Person can born with mutations. So, genetic conditions can cause mutations.
And Second - acquired mutations during lifetime.
Carcinogens are environmental factors which can cause mutations in the genome.
Carcinogens can be chemicals, viruses or radiation.
Mutation can be several Types:
Overexpression:
Means hyperactivity or unregulated activity of the gene.
Point mutation.
Occurs when a single nucleotide is changed, Inserted or deleted from a DNA. Result of point mutation can be different:
Gene can be activated or deactivated. Change function, or no effect at all.
Translocation;
Gene fragment translocate to another site and activates the gene next to it.
Amplification.
mutation in which you getting multiple copies of gene. So its function increases.
Insertion.
Additional information is added to genome for example, by virus.
These mutations can be happened in different sites of genome. And they affect different function of cell and alter normal function of the cell.
Three common areas exist in which mutation causes cancers.
1. Mutation of Growth promoting genes. Which are called Proto oncogenes.
This protooncogenes we have normally, they are required for normal tissue growth.
If proto oncogenes are mutated and they are not normal anymore, they are called oncogenes.
Oncogenes causes synthesis of new proteins, which called growth factors. And they act like signal for cells to start, uncontrolled proliferation. and cancer is formed.
For example amplification of ERBB2 oncogene, causes Breast, ovary and lung cancers.
The product of the oncogene is Epidermal growth factor receptor. When grow factor receptor quantity increases on the cell membrane, grow factor impacts cells function. and cell starts proliferation, eventually we get cancer.
2. Mutation the gene which inhibits cells uncontrolled growth; called tumor suppressor genes.
In contrast with protooncogenes, where their overexpression, activation and amplification causes cancer, in case of Tumor suppressor genes, should inactivated, they should loss their function to cause cancer.
P53 is classical example of tumor suppressor gene.
Normally, If the cell is damaged, P53 gene stops the cell from uncontrolled proliferation. It arrests the cell cycle.
Tumor suppressor genes are located on both chromosomes. And 2 mutation is needed to stop them from functioning.
According to two hit hypotheses, tumor suppressor on one chromosome can be inactivated congenitally.
Another one can be inactivated by environmental factors. For example: Chemicals, or radiation.
Example of tumor suppressor gene mutation is:
Li-Fraumini syndrome - (in which germline mutation of TP53 on chromosome 17 is associated with a high rate of many types of tumors).
3. Mutation The genes which regulates apoptosis can cause cancer. Moreover, mutation the gene which prevents apoptosis can cause cancer.
Normally if cell DNA is damaged and it has risk developing cancer it suicide itself to save organism from potential cancer development.
Such action is called apoptosis, and is regulated by apoptotic genes.
But sometimes they are inactivated, or prevented by other genes overexpression.
For example:
Normally, Bcl-2 prevents apoptosis (programmed cell death).
In the follicular lymphomas, Bcl-2 regulator of apoptosis is overexpressed, due to translocation mutation.
Resulted lymphocytes fail to die as expected and instead produce a tumor.
By Thomas Splettstoesser - Based on atomic coordinates of PDB 1TUP, rendered with open source molecular visualization tool PyMol (www.pymol.org), CC BY-SA 3.0, https://commons.wikimedia.org/w/index...
By Simon Caulton - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index...
Carcinogenesis would not happen without mutation.
Mutation is an alteration in the genome of an organism.
A single mutation is not enough, to develop cancer.
It requires, several mutations in the genome.
There are two main sources to get mutation.
First. Person can born with mutations. So, genetic conditions can cause mutations.
And Second - acquired mutations during lifetime.
Carcinogens are environmental factors which can cause mutations in the genome.
Carcinogens can be chemicals, viruses or radiation.
Mutation can be several Types:
Overexpression:
Means hyperactivity or unregulated activity of the gene.
Point mutation.
Occurs when a single nucleotide is changed, Inserted or deleted from a DNA. Result of point mutation can be different:
Gene can be activated or deactivated. Change function, or no effect at all.
Translocation;
Gene fragment translocate to another site and activates the gene next to it.
Amplification.
mutation in which you getting multiple copies of gene. So its function increases.
Insertion.
Additional information is added to genome for example, by virus.
These mutations can be happened in different sites of genome. And they affect different function of cell and alter normal function of the cell.
Three common areas exist in which mutation causes cancers.
1. Mutation of Growth promoting genes. Which are called Proto oncogenes.
This protooncogenes we have normally, they are required for normal tissue growth.
If proto oncogenes are mutated and they are not normal anymore, they are called oncogenes.
Oncogenes causes synthesis of new proteins, which called growth factors. And they act like signal for cells to start, uncontrolled proliferation. and cancer is formed.
For example amplification of ERBB2 oncogene, causes Breast, ovary and lung cancers.
The product of the oncogene is Epidermal growth factor receptor. When grow factor receptor quantity increases on the cell membrane, grow factor impacts cells function. and cell starts proliferation, eventually we get cancer.
2. Mutation the gene which inhibits cells uncontrolled growth; called tumor suppressor genes.
In contrast with protooncogenes, where their overexpression, activation and amplification causes cancer, in case of Tumor suppressor genes, should inactivated, they should loss their function to cause cancer.
P53 is classical example of tumor suppressor gene.
Normally, If the cell is damaged, P53 gene stops the cell from uncontrolled proliferation. It arrests the cell cycle.
Tumor suppressor genes are located on both chromosomes. And 2 mutation is needed to stop them from functioning.
According to two hit hypotheses, tumor suppressor on one chromosome can be inactivated congenitally.
Another one can be inactivated by environmental factors. For example: Chemicals, or radiation.
Example of tumor suppressor gene mutation is:
Li-Fraumini syndrome - (in which germline mutation of TP53 on chromosome 17 is associated with a high rate of many types of tumors).
3. Mutation The genes which regulates apoptosis can cause cancer. Moreover, mutation the gene which prevents apoptosis can cause cancer.
Normally if cell DNA is damaged and it has risk developing cancer it suicide itself to save organism from potential cancer development.
Such action is called apoptosis, and is regulated by apoptotic genes.
But sometimes they are inactivated, or prevented by other genes overexpression.
For example:
Normally, Bcl-2 prevents apoptosis (programmed cell death).
In the follicular lymphomas, Bcl-2 regulator of apoptosis is overexpressed, due to translocation mutation.
Resulted lymphocytes fail to die as expected and instead produce a tumor.
By Thomas Splettstoesser - Based on atomic coordinates of PDB 1TUP, rendered with open source molecular visualization tool PyMol (www.pymol.org), CC BY-SA 3.0, https://commons.wikimedia.org/w/index...
By Simon Caulton - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index...
3 سال پیش
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