Tut 2: DNA and cell division (Metastatic cancer) Flashcards
What are the stages of cell division and the cell cycle?
M phase - Mitosis (nuclear division) and cytokinesis (cytoplasmic division)
G1 phase - Growth and checking phase.
S phase - DNA replication: duplication of chromosome producing 2 x sister chromatids.
G2 phase - Growth and checking phase.
What is the genetic code?
The genetic code is the language that translated the sequence of nitrogenous bases in the mRNA into the amino acids of a protein. One codon/triplet specifies one amino acid.
Explain the steps associated with mitotic division
Prophase - Break down of the nuclear membrane, formation of spindle fibres and the condensing of chromosomes.
Prometaphase - Spindle fibres attach to chromosomes and chromosomes continue to condense.
Metaphase - Alignment of chromosomes
Anaphase - Centromeres divide and the sister chromatids move to opposite poles.
Telophase - The nuclear membrane reforms, chromosomes decondense and the spindle fibres disappear
Cytokinesis - The cytoplasm divides and the parent cell becomes 2 daughter cells with identical genetic information
Explain the regulation of the cell cycle.
The cell cycle consists of checkpoints to ensure that incomplete/damaged chromosomes are not replicated and passed onto daughter cells. In the G1 phase checkpoint, apoptosis can occur if DNA is damaged and it unable to be repaired. In the G2 phase checkpoint, mitosis will not occur if DNA is damaged/not replicated. At the M phase checkpoint, mitosis stops if the chromosomes are not properly aligned.
What can go wrong with DNA sequences?
Alterations in DNA sequences can lead to mutations. Mutations are often caused by chemical/physiological agents and errors during DNA replication. Mutations can be inherited from parents. Normally, cells can repair these mistakes with the use of DNA repair genes, but if they are not repaired, these alterations are made permanent when the cell is replicated. Normally, if the DNA can’t be repaired, the cell will undergo cell death through apoptosis.
Alterations in primary DNA sequences can be harmless or potentially lead to a loss of protein function.
Explain apoptosis
Apoptosis is the pathway that a cell undergoes for programmed cell death.
This pathway is triggered by an external stimulant such as death receptors. Once the cell is signalled to die, it makes proteases to degrade the components of the cell. Eventually macrophages engulf cellular remains and debris. It is a common pathway used for old/damaged cells.
What are the 6 classical hallmarks of cancer cells?
- Sustaining proliferative signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing angiogenesis
- Resisting cell death
Explain how normal growth is lost in cancer.
Cancer cells can learn how to grow and thrive in the absence of growth stimulatory signals and become insensitive to antigrowth signals, hence are able to grow unchecked, producing more and more cancer cells. One mutation is not enough to cause cancer because there are so many methods that can be used to overcome it I.e. DNA repair mechanisms, cell apoptosis and the immune system. For a cell to become malignant, it requires at least 6-7 gene mutations.
Cancer cells are also able to learn how to avoid the apoptotic pathways, and hence don’t die when they should, leading to cancer.
Explain how cancer cells undergo uncontrolled cell division
Proteins that promote cell division are encoded by proto-oncogenes. Mutations to oncogenes, when switched on stimulate the production of cell growth proteins –> Cancer.
Also, proteins that inhibit cell division can be encoded by tumour suppressor genes that turn off these genes, hence allowing more cell divisions to occur –> Cancer.
Explain how a cell goes from being benign to cancerous.
Uncontrolled division and disruption of normal cell organisation/tissue architecture can lead to a carcinoma.
Cells can become motile and learn how to spread and establish colonies through inactivation of controls that normally confine a cell to the site and tissue where is normally grows –> metastasis
What are the types of mutations that need to occur to cause a metastatic disease?
Mutations inactivate suppressor gene causing cells to proliferate. Mutations then inactive DNA repair genes, proto-oncogenes mutate into oncogenes leading to more mutations and hence more genetic instability resulting in metastatic disease.
Begning tumour cells can only grow locally and can’t spread by invasion or metastasis. However malignant cells invade neighbouring tissues, enter blood vessels and metastasise to different sites of the body.
List some of the ways that DNA mutations can occur.
Radiation, Viruses, Chemicals, Diet hormones, hereditary
Genes that are implicated in cancers include: Oncogenes, tumour suppressor genes, DNA repair genes, Cell death genes, Cell cycle checkpoint genes etc.
What are some of the cancer therapies available?
Surgery, Radiation therapy, Chemotherapy and novel therapies.
