Cancer Cells Flashcards
Give an overview of cancer cells?
A tumour can be benign if it hasn’t invade other cells but if it metastasises then it is cancerous and is considered malignant
Metastases are secondary tumours forming at other sites in the body
They develop gradually from increasingly aberrant cells - through varying stages
There are often successive rounds of random mutations leading to natural selection of ‘favourable’ mutations causing increasingly worse cancer
Most cancers derive from a single abnormal cell - primary cell
Cancer cells contain somatic mutations and they need more than a single mutation to cause cancer
They are genetically unstable - accumulating gross abnormalities in the karyotype
What can cancer cells be defined by?
- They reproduce in defiance of normal restraints of cell growth/division
- They invade/colonise territories of other cells
How do we classify cancer cells?
This depends on the tissue it invades:
Carcinoma - arise in epithelial cells (most common)
Sarcomas - arise from connective tissue/muscle cells
Leukaemia/lymphoma - derived from white blood cells and cells of the nervous system
What are the hallmarks of cancer?
Self-sufficiency in growth signals Insensitivity to anti-growth signals Tissue invasion and metastasis Limitless replicative potential Sustained angiogenesis Evading apoptosis
What are the major processes affected in cancer developement?
- Cell cycle - excessive cell proliferation
- Programmed cell death (apoptosis) is reduced resulting in a greater rate of cell survival
- Cell adhesion is impaired - allowing tumour cells to detach from the tissue of origin
- Angiogenesis - formation of new blood vessel which deliver oxygen and nutrients for tumour growth
What is the mammalian cell cycle and how is it involved in cancer cells?
S phase - where DNA is synthesised
Mitosis
G1 and G2 - gap phases (preparation for S phase or mitosis)
There are checkpoints in the cell cycle to make sure everything is favourable to move onto the next phase
If not favourable the cycle is stalled until this can be repaired
Describe cancer as a genetic disease?
- Genetic changes (mutations) are the cause of cancer (some are inherited but the majority are sporadic)
Many mutations arise from genetic instability - Mutations in several genes (5-7) in a single cell are involved
- Examples of mutations occurring in cancer:
Point mutations, e.g. ras protein, GLY to VAL (codon 12)
Amplification (many copies of a gene): myc - leads to increased production of cell growth
Deletions
Chromosomal re-arrangements, e.g. translocations
What is another origin of cancer?
Cancer stem cells
Cancer cells that can self-renew to produce more malignant stem cells and at the same time generate non-tumorigenic cells - such as transit amplifying cells
What are epigenetic factors?
This is a change in gene expression
Expression of genes (including those involved in cancer) can be influenced by :
methylation of specific C ( cytosine/s) in promoters
Changes in chromatin structure independent of DNA – chromatin remodelling caused by e.g. post-translational modifications in histones such as acetylation/deacetylation
What are the major types of genes/proteins that are involved in cancer?
- Oncogenes/oncoprotein - pro-growth
- Tumour suppressor genes/proteins - growth suppressing
- DNA maintenance genes (involved in DNA repair) - errors go undetected, giving rise to mutations
What are the different mutation types on cancer causing disease?
Dominant mutation - gain of function
Single mutation event in proto-oncogene = oncogene
Oncogenes stimulate excessive cell survival and proliferation
Recessive mutation - loss of function
Mutation event - inactivates tumour suppressor gene (no effect in gene copy)
Second mutation event - inactivated second gene copy
This completely eliminates the tumour suppressor gene = excessive cell survival and proliferation
Describe proto-oncogenes into oncogenes?
Mutation in coding sequence - DNA, RNA, hyperactive protein made in normal amounts
Gene amplification - DNA, RNA, normal protein greatly overproduced
Chromosome rearrangement (e.g. Promotor) - two outcomes:
Nearby regulatory DNA sequence causes normal protein to be overproduced
Fusion to actively transcribe gene produces hyperactive fusion protein
Certain viruses (retroviruses) can acquire proto-oncogenes from the cellular genome and convert them into viral oncogenes
What are the functions of the proto-oncogenes?
Growth factors (e.g. platelet-derived growth factor)
Growth factor receptors (e.g. epidermal growth factor receptor)
Signal transducers (e.g. ras-GTPase)
Nuclear proto-oncogenes and transcription factors (e.g. c-myc transcription factor)
Describe tumour suppressors?
Mutation in a tumour suppressor gene causes a loss of gene function
Both copies of the tumour suppressor gene need to be inactivated by mutation to create a cancer cell - as they are recessive genes
Some DNA viruses (e.g. HPV) bind tumour suppressor gene products and inactivate or degrade them - proteolysis
Genetic and epigenetic mechanisms can inactivate them
What does the Rb gene do?
Rb - regulates between G1 and the S-phase
If mutations then this checkpoint isn’t regulated and cells proceed faster around the cycle
Any mutations acquire during the G1 phase will be passed into the S phase and will be replicated
