Biology 1 What is cancer? Flashcards
Define cancer
The uncontrolled growth of abnormal cells in the body. Cancerous cells are also called malignant cells.
What balance shift occurs in cancer?
The balance between cell proliferation and apoptosis (cell death) shifts to proliferation and cell survival leading to an accumulation of cells.
How do cells accumulate?
Abnormal cells accumulate due to increased division in abnormal cells and a decrease in cell death.
How is cell division controlled?
Genes control cell division in response to environmental clues that tell the cells whether to divide, die or do neither.
What happens in mutations?
Mutations are changes to genetic information over time I.e the addition, removal or substitution of nucleotides. The changes can be harmful, beneficial or neutral.
Consider the analogy of a sinfonia orchestra - slight changes to each individual note often are silent and unobserved but if lots of individual notes begin to deviate from the norm then it can have a profound affect.
What do proto-oncogenes do?
They encode proteins that increase cell division and proliferation and reduce cell death ; we need them to proliferate normally.
What are tumour suppressor genes?
They encode proteins that reduce cell division and proliferation and induce cell death via apoptosis.
What are DNA stabilising genes?
Often included in the tumour suppressor category, the genes encode for proteins that maintain DNA stability by repairing DNA and protecting against accumulation of mutations (if the protein cannot be repaired then it is programmed for apoptosis (cell suicide)). Without these stabilising repair genes then the effect of a mutation could cause runaway proliferation of the abnormal cell and lead to cancer.
Car Analogy
In the development of cancer the proto-oncogene is the accelerator. An oncogene is a faulty accelerator that cannot be stopped. Tumour suppressor genes are the brakes and a mechanic offers the role of stability (DNA stabilising genes). Without the brakes or stabilising mechanic the oncogene becomes a greater problem.
When considering the hallmarks of cancer biology which 6 areas can be covered?
Sustaining proliferation signalling Evading growth suppressors Activating invasion and metastasis Enabling replicative immortality Inducing angiogenesis Resisting cell death
How is proliferation cell signalling sustained?
The careful control of proliferation in normal cells is managed by processes that are deregulated (receptors and signalling pathways interrupted). Checkpoints in the cell cycle are also disabled so that profliferation continues that would otherwise be stopped by the checkpoint.
Additionally, pro-growth factored are unregulated I.e. Extra ligand, constitutive activation of receptors and mutations in the signalling pathways.
Which are the two main tumour suppressors?
p53 (TP53, tumour protein 53 known as
the guardian of the genome) and RB1 (retinoblastoma 1)
How does p53 act as a tumour suppressor?
Blocks the cell cycle in response to cellular damage and induces apoptosis in cells with DNA that cannot be repaired. It is a transcription factor that leads to changes in gene expression which is most commonly mutated so that it doesn’t work in cancer hence unregulated proliferation in cells that should be programmed for apoptosis.
What is RB1s role as a tumour suppressor?
Blocks the cell cycle by binding and inhibiting E2F transcription factors that are needed for cell cycle progression (hence stopping the cell cycle). It is not s transcription factor itself unlike p53 but it inhibits other transcription factors.
Which are the two main proto-oncogenes subject to mutation in cancer?
MYC - a transcription factor that promotes cell growth and leads to changes in gene expression
RAS - a family of G proteins that binds either GDP (inactive) or GTP (active). The G proteins are activated by growth factors that activate a downstream signalling pathway. This can lead to changes in gene expression.
