Carla: Role of Cell Signalling In Disease Flashcards
List some positive cues for cell cycle progression
(4)
Growth factors
Signalling molecules e.g. small peptides or proteins
Interactions with intracellular signalling pathways via hormones
Other small molecules -> mitogens
What do positive cues for progression do exactly?
They increase the activity of cyclins and Cdks
How do signalling molecules such as small peptides and proteins act as signalling cues?
(3)
Signalling molecules are detected by receptors
Signal transduction within the cell occurs
This brings about a response
Give an example of a small peptide signalling cue
Cytokines
Give an example of a positive progression cue cytokine
Granulocyte-macrophage colony-stimulating factor
Give three examples of positive cue signalling proteins
VEGF
EGF
PDGF
What type of hormones act as positive cues
Steroid hormones
Give three examples of types of steroid hormones that act as positive cues
Estrogen
Androgens
Progesterones
What are small molecules that act as positive cues called?
Mitogens
Give an example of a mitogen
ROS
List four negative cues for progression
DNA damage
Retinoblastoma protein Rb
p53
p21
What do negative cues actually do?
Decrease the activity of cyclins and Cdks
Where exactly do negative cues act?
The G1checkpoint
What is p53 often called?
The Guardian of the Genome
Why is p53 known as the Guardian of the Genome
(2)
It conserves stability by preventing genome mutation
The TP53 gene is classified as a tumour suppressor gene
Give three roles of p53
Triggers CDK1 proteins at G1
Activates DNA repair proteins
Programmed cell death
(Overall it maintains genomic stability)
Give two other names for p53
Tumour protein 53 (TP53)
Phosphoprotein 53
Where is the TP53 gene found?
Short arm of chromosome 17
Ch17p13.1
How long is the TP53 gene?
20,000 bp long
What can stimulate the expression of TP53?
UV light
What effect does p53 have on stem cells?
Important role in the regulation of stem cells
p53 levels are maintained at low inactive levels in human embryonic stem cells (hESCs)
p53 activation leads to rapid differentiation of hESCs
What does hESC stand for
Human embryonic stem cells
What two things will activated p53 do?
Cell will either enter cell cycle arrest
OR
Undergo apoptosis
What happens if p53 puts a cell cycle into arrest?
DNA will be repaired
Cell cycle will be restarted
Cellular and genetic stability is restored
What happens if activated p53 puts a cell into apoptosis?
(2)
Cell death and elimination of damaged cells will occur
Cellular and genetic stability is restored
What are the two common traits in all cancer?
Abnormal cells
Out of control growth
What four things can abnormal function of cells lead to?
Uncontrolled growth
Increased division
Decreased death
Other aberrant characteristics of cancer cells
What are the three characteristics of malignant cancer cells?
Uncontrolled cell growth
Invasion
Sometimes metastasis
What classifies as uncontrolled cell growth?
Division beyond the normal limits
What classifies as invasion?
Intrusion on and destruction of adjacent tissues
What classifies as metastasis
Spread to other locations in the body via lymph or blood
What are benign cancers?
Tumours which are self-limited
They do not invade or metastasize
Write a note on cancers
(5)
Can affect all animals
Can affect people of all ages including foetuses
For most varieties risk increases with age
Nearly all are caused by abnormalities in the genetic material of the transformed cells
Most form a tumour but some don’t e.g. leukaemia
Categorise cancers
Carcinoma
Sarcoma
Lymphoma and leukaemia
Germ cell tumour
Blastic tumour/blastoma
What are carcinomas?
(3)
Malignant tumours derived from epithelial cells
Most common cancers
e.g. breast, prostate, lung and colon cancers
What are sarcomas?
Malignant tumours derived from connective tissue or mesenchymal cells
What are lymphomas and leukaemia?
Malignancies derived from hematopoietic cells
What are blood formoing cells called?
Hematopoietic cells
What are germ cell tumours?
(3)
Tumours derived from totipotent cells
In adults these are often found in testicles/ovaries
In foetuses/babies/kids most often found on the body midline, particularly tip of the tailbone
What are totipotent cells?
Stem cells that have the potential to develop into any cell found in the human body
What are blastic tumours/blastomas?
(2)
A usually malignant tumour which resembles an immature or embryonic tissue
Many of these tumours are most common in children
Classify hallmarks of cancer
Enabling hallmarks
Primary hallmarks
Emerging hallmarks
What are the two enabling hallmarks of cancer?
Genomic instability and mutation
Tumour promoting inflammation
What are the six primary hallmarks of cancer?
Invasion and metastasis
Evading growth suppressors
Replicative immortality
Resisting cell death
Sustained proliferation signal
Inducing angiogenesis
What is angiogenesis?
The development of new blood vessels
What are the two emerging hallmarks of cancer?
Evading immune destruction
Reprogramming Energy Metabolism
How is cancer lethal?
(5)
Replacement of function with non-functional
Weakened immunity -> infections
Haemorrhaging
Tumour burden
Overall stress on heart, digestive system and kidneys
What is meant by tumour induced haemorrhaging?
(3)
Tumours induce angiogenesis -> development of new blood vessels
The invading cells have an increased need for vasculature
This vasculature can intwine regular vasculature and cause a haemorrhage
What is mean by tumour burden?
Tumour size and location can effect the function of an organ and the blood flow to the organ
What is the genetic basis of cancer?
(6)
Amplification or activating mutation in oncogenes
Loss or inactivating mutation in gene involved in tumour suppressor genes TSGs
Generation of a fusion gene with cell cycle promoting activities
Alterations in promotor activity
Loss or inactivating mutation in a gene involved in DNA repair or apoptosis
Viral involvement
What are oncogenes?
Genes involved in promoting cell division
What are tumour suppressor genes?
Genes involved in halting cell division
How do tumours induce angiogenesis?
(4)
Tumour proliferates and causes hypoxia
Hypoxia induces expression of VEGF
VEGF stimulates angiogenesis
=> rapid tumour growth and metastasis
What molecule induces angiogenesis?
(2)
VEGF
Vascular endothelial growth factor
What is the typical route of metastasis?
(6)
Tumour forms
Cells become invasive and enter capillary
Cells travel through bloodstream
1 in 1000 cells survive and adhere to blood vessel wall in other organs
Cells escape from blood vessel to form micrometastasis
Cells colonise liver forming full-blown metastasis
