Cancer and cell cycle Flashcards
Define cancer
A neoplastic disease, the course of which is often fatal (malignant neoplasm)
Malignant growth resulting from uncontrolled proliferation of cells
What are the main phases of the cell cycle and how are they divided?
Interphase: divided into G1, S and G2
Mitosis
Describe what happens in G1, S and G2? How long does each stage last for?
G1: Cell growth, copies of organelles are made and new proteins are made (10 hours)
S: DNA replication (7.5 hours)
G2: Growth of cells, synthesis of new proteins and copies of organelles (3.5 hours)
How long does Mitosis last for and describe it?
Mitosis: process of cell division to form two new daughter cells (1 hour)
What stage of the cell cycle is mitogen dependant?
G1: eternal environment is monitored for signals e.g. growth factors
What is the G0 phase?
Quiescent stage - whereby cells are not dividing but are active
What cells are permanently in G0 phase?
Erythrocytes
How many cell cycle checkpoints are there, when do they occur and what do they assess for?
4 checkpoints:
Restriction point: near the end of G1, monitors cell size and favourable environmental conditions (nutrients and growth factors)
G1/S: checks for DNA damage
G2/M: checks that DNA has replicated properly and for DNA damage
M: checks for chromosome attachment to spindle fibres and alignment along metaphase plate
What 2 things is progression through the cell cycle controlled by?
Cyclins
Cyclin Dependant Kinases (CDKs)
What is the role of Cyclins? What are the types?
Regulate CDKs Cyclins are present throughout the stages of the cell cycle but eat during the stage they are needed at. Cyclin D Cyclin E Cyclin A Cyclin B (Maturation promoting factor)
What is the role of CDKs and how are they activated?
CDKs are usually inactive and become activated by Cyclin proteins. Once activated, they are directed at specific target proteins. They phosphorylate proteins and if enough phosphorylation occurs then they stimulate the cell cycle and allow progression to the next stage.
What happens if insufficient phosphorylation of proteins occur by CDK?
Then cells enter the G0 phase and don’t proceed past the checkpoint
What is needed for cell proliferation?
Process of signal transduction and extracellular signal
Explain process of cell proliferation?
Extracellular signal (ligand) binds to receptor on plasma membrane. Signal is transduced and target of signal transduction pathway is a downstream molecule: often a transcription factor which regulates gene expression. transcription factor receives signal and it becomes activated and goes into nuclei. TF regulates 2 target genes: Cyclins and DNA polymerase
What cause unregulated cell proliferation? Give e.g.
Activation of oncogenes e.g. RAS and MYC genes
Inactivation of tumour suppressor genes e.g. p53
Constitutive expression of telomerase which leads to immortalisation of cell
What are proto-oncogenes?
Normal, non-mutated genes which code for proteins that help regulate cell growth and differentiation.
What are oncogenes?
These are mutated photo-oncogenes and positive cell cycle regulators. They have malignant properties and are overactive genes
What effect do oncogenes have?
As they are are overactive genes, they cause uncontrolled cell growth and bypass of cell checkpoints.
What are tumour suppressor genes? What is their role?
Negative cell cycle regulators.
How do tumour suppressor genes halt cell cycle and what is the role of p53?
In normal cells, if DNA damage occurs then cell cycle will be halted and p53 TF will be produced. p53 reads DNA and makes proteins for arrest of cell cycle e.g. p21 which is a CDK inhibitor. If DNA repair does not occur, levels of p53 keep rising and it switches on pro-apoptotic genes and apoptosis occurs.
Why is it a problem if p53 is inactivated in cancer cells ?
Cell arrest, DNA repair and apoptosis do not occur. SO cells can bypass all the checkpoints and grow uncontrollably.
Give examples of external factors for growth
Hormones
Peptide Growth factors
Give an example of cell surface receptors for growth?
EGFR
What are the two types of malignant genes that oncogenes can code for?
Hyperactive version of normal gene product
Normal protein but over expression, wrong time or in wrong cell type
What mutations cause hyperactive proteins?
Point mutation
Deletion
Chromosomal translocation
What is the Philadelphia translocation?
Rearrangement of Bcr and Abl gene to permanent switch on TRK and cause constant cell proliferation
What mechanisms cause normal gene but either over expression, wrong time or in wrong cell type?
Gene amplification
Chromosomal rearrangement
What is retinoblastoma protein?
A tumour suppressor gene and transcription factor inhibitor
What is the role of Rb and what happens if cell receives a signal to grow?
Rb inhibits transcription factors e.g. E2F and DP1.
If cell receives a signal to grow, then CDKs are activated. When Rb is sufficiently phosphorylated it moves way from the complex it forms with TFs. TFs are free to switch on gene expression.
What is the role of telomeres? how do they achieve this?
Little bit of telomere is rubbed off during each cell division. telomeres restrict the ability of a cell to divide by preventing end to end fusion of chromosomes.
What is the function fo the enzyme, telomerase ? what does this lead to?
It adds a bit of telomer back on which leads to unlimited cell division and constitutive telomerase expression
Which cyclins interact with which CDKs during which checkpoints of the cell cycle?
Restriction point/G1: Cyclin D and CDK 4/6
G1/S: Cyclin E and CDK 2
G2/M: Cyclin A and CDK 2
M: Cyclin B and CDK 1
What are the two ways in which CDK inhibitor can work?
Acting as a Competitive CDK ligand
Forming an inactive complex
Describe the stages of mitosis
Prophase: Nuclear membrane disintegrates. Chromosomes condense and becomes visible as 2 paired chromatids.
Spindle fibres attach at kinetochores at centromeres of chromosomes.
Metaphase: Spindle fibres align the chromosome along the metaphase plate
Anaphase: Spindle fibres pull on chromosomes and start to pull them apart
Telophase: Chromosomes are pulled to opposite poles of the cell. Chromosomes uncoil and nuclear membrane reappears.
Cytokinesis: cytoplasm splits into two daughter cells
