Oncogenes and Tumour Suppressor Genes Flashcards
What are the major functional changes in cancer?
- Increased growth: loss of growth regulation, stimulation of environment promoting growth e.g. angiogenesis
- Failure to undergo programmed cell death (apoptosis) or senescence
- Loss of differentiation: including alterations in cell migration and adhesion
- Failure to repair DNA damage: including chromosomal instability
Summarise function of oncogenes and tumour suppressors
Oncogenes: Gain of function
Tumour Suppressor: Loss of function
Oncogene
- An altered gene whose product can act in a dominant fashion to help make a cell cancerous. Oncogene is a mutant form of a normal gene involved in the control of cell growth or division.
- Any cellular gene that upon activation can transform cells.
Tumour Suppressor Gene
A gene whose normal activity prevents formation of cancer. Both genes for the tumour suppressor must be mutated. Loss of this function by mutation enhances the likelihood that a cell can become cancerous.
Mutations in Oncogenes
Gain a mutation in one of the alleles will activate the gene.
Mutations in Tumour suppressors
Gain a mutation in one allele but not enough to have an effect. Need two mutations - one in each allele.
Examples of oncogenes
MyC
Ras - normal cell growth signaling pathways
Examples of tumor suppressors
Rb - retinoblastoma
p53 - the guardian of genome
How is an oncogene created?
During evolution, the virus can acquire fragments of genes from the host at integration sites and this process results in the creation of oncogenes.
Bishop and Varmus ‘The Oncogene Hypothesis’
- Identified the v-src oncogene as responsible for causing cancer
- Used hybridization experiments, and found c-src gene present in many species
- C-src involved in the positive regulation of cell growth and cell division.
- Following infection, the v-src oncogene was expressed at high levels in the host cell, leading to uncontrolled host cell growth, unrestricted host cell division, and cancer.
- When proto-oncogenes are exposed to carcinogens (various agents) may transform cells by ‘switching on’ the endogenous oncogenic information.
Which virus are most of us infected with?
Epstein-Barr virus
What percentage of cancers are caused by oncoviruses?
15-20%
How are viral oncogenes transmitted?
By either RNA or DNA viruses
How do DNA viruses infect cells?
They cause lytic infection leading to the death of the cellular host or can replicate their DNA along with that of the host and promote neoplastic transformation.
How do DNA viruses initiate and maintain tumours?
Encode various proteins along with environmental factors
How do RNA viruses induce cancer?
Integrate DNA copies of their genomes into the genome of the host cell and as these contain transforming oncogenes they induce cancerous transformation of the host.
What is LMP-1?
An oncogene produced by the Epstein-Barr virus that is always switched on and feeds into pathways pushing survival the cell to tumourigenesis.
What type of activations can oncogenes undergo?
Mutations, Insertions, Amplifications, and Translocations which lead to the loss of response to growth regulatory factors. One allele needs to be altered.
What are the 4 types of proteins involved in the transduction of growth signals?
- Growth factors
- Growth factor receptors
- Intracellular signal transducers
- Nuclear transcription factors
Proto-oncogenes encode components of the growth factor signal transduction pathway.
The function of oncogene proteins
The majority of oncogene proteins function as elements of the signalling pathways that regulate cell proliferation and survival in response to growth factor stimulation.
