molecular basis of cancer Flashcards
what are important characteristics of cancer cells?
- replicative immortality
- inducing angiogenesis
- metastasis
- high rate of cell division
- genome instability & mutation
- loss of anchorage dependence
- lack of contact inhibition & density-dependent inhibition
- avoid immune destruction
why do cancer cells have replicative immortality?
- in most cancer/tumour cells, telomerase genes are reactivated, so telomerase is produced and maintains telomerase lengths so that the cancer cells divide indefinitely/are immortalised.
- whereas in most somatic cells, telomerase genes are switched off so they can only divide a limited number of times
- telomerase allows cancer cells to evade apoptosis
what is angiogenesis and its significance in cancer development?
- ☆ angiogenesis is the process by which new blood vessels are formed. it is a tightly regulated process which occurs only when necessary, such as growth or repair. abnormal regulation may result in diseases like cancer
- to develop into larger, potentially metastatic tumours, a growing tumour stimulates the formation fo new blood vessels, or angiogenesis.
- these blood vessels increase blood flow to the tumour, supplying nutrientsand oxygen and removing toxic waste products. they also provide pathways for cancer cells to spread to other sites in the body.
- to stimulate the formation of new blood vessel, a tumour cell expresses angiogenesis-activating protein genes to produce angiogenesis activating proteins
what is metastasis and its significance in cancer development?
- ☆ metastasis is a process where the primary tumour cells invade local tissues & blood vessels, establishing secondary tumours called metastases at distant sites.
- cancer cells invade surrounding tissues and penetrate through the walls of lympathic & blood vessels, gaining access to the bloodstream. cancer cells are then transported by the circulatory system throughout the body. cancer cells then leave the bloodstream and enter particular organs, where new secondary tumours at distant sites from the primary tumour are established
what are benign and malignant tumours?
- benign tumours have few genetic mutations and do not cause serious health problems. they could be completely removed by surgery
- malignant tumours are invasive and could impair functions of organs. individuals with malignant tumours are considered to have cancer. systemic treatment like radiation or chemotherapy is required in conjunction with surgery to ensure complete eradication of all malignant tumour cells
what are cell cycle checkpoints and their role in preventing cancer?
- ☆ cell cycle checkpoits are critical control points where stop & go ahead signal can regulate the cycle. checkpoints ensure the orderly progression of the cell cycle; if a malfunction occurs, signals are sent to the control system to delay progression into the next phase
what are the differences between benign & malignant tumours?
shape & differentiation ⮕ benign tumour cells have SMALL & REGULARLY-shaped nucleus, and are well-differentiated. malignant tumour cells have LARGE and IRREGULARLY-shaped nucleus, and are poorly-differentiated.
nuclear:cytoplasmic volume ratio ⮕ benign tumour cells have low nuclear:cytoplasmic volume ratio while malignant tumour cells have high nuclear:cytoplasmic volume ratio (i.e. have big nucleus compared to cell)
rate of mitosis ⮕ benign tumour cells have LOW rate of mitosis compared to malignant tumour cells that have HIGH rate of mitosis
tumour boundary ⮕ benign tumour cells have a well-defined tumour boundary as tumour cells remain clustered together with a well-defined perimeter. malignant tumourcells have a poorly-defined tumour boundary as tumour cells may not cluster together due to their ability to metastasise
what are the 3 cell cycle checkpoints?
not the most important
- G1 checkpoint (assessment of cell growth) ⮕ checks for: growth factors (signal molecules), DNA damage, cell size & nutrients. apoptosis occurs if DNA is damaged & cannot be repaired
- G2 checkpoint (assessment of DNA replication) ⮕ checks if DNA is replicated successfully without damage. apoptosis occurs if there is irreparable damage
- M checkpoint (assessment of mitosis) ⮕ occurs at metaphase and checks if there is successful formation of spindle fibres & attachment of spindle fibres to the kinetochores of chromosomes. if spindle fibres are not formed or attachment is inadequate, mitosis is arrested
what are cyclin-dependent kinases (Cdks) and what do they do in the cell cycle?
- cyclin-dependent kinases, Cdks, phosphorylate their substrates by transferring phosphate groups from ATP to the substrates.
- Cdks need to be bound to cyclin to be activated, forming cyclin-Cdk complexes that are also called maturation-promoting factor (MPF)
- MPFs promote mitosis by phosphorylating substrates that control the orderly progression of the cell cycle
- in many cancers, when cell cycle control genes like cyclin and/or Cdk genes are mutated, this results in the over-expression of cyclins & Cdks. cells that have escaped precise cell cycle control can proliferate indefinitely.
what is the function of a tumour suppressor gene?
tumour suppressor genes are a family of normal genes that code for proteins that prevent uncontrolled cell division ⮕ loss of such proteins allows a cell to divide through the absence of suppression in cell division
functions of tumour suppresor proteins (coded for by tumour suppressor genes)
1. take part in cell signalling pathways to inhibit the cell cycle
2. halt cell division if DNA is damaged (cell cycle arrest)
3. triggers DNA repair mechanisms, preventing cells from accumulating DNA damage
4. initiate apoptosis if DNA damage cannot be repaired
5. maintain cell-to-cell adhesion
what kind of mutation ?
under what circumstances will no functional gene product be produced by tumour suppressor genes?
a loss of function mutation, defined as a mutation that results in abolished protein function, must occur.
if one copy of a tumour suppressor gene is lost, cell cycle activity remains normal as the other copy of the gene is still able to produce sufficient quantityof the normal gene product to regulate the normal cell cycle.
so in order to abolish the function of TSGs totally, both copies of the TSG must be mutated so that no functional gene product can be produced.
this is a loss of function mutation, and mutated TSGs act in a recessive manner (since both copies need to be mutated)
what is an example of a tumour suppressor gene?
the p53 gene is a tumour suppressor gene.
it is critical as it is involved in apoptosis, maintenance of genetic stability AND cell cycle control
describe the role of p53 protein (coded for by p53 gene) in the cell cycle and how it prevents cancer.
p53 protein is a transcription factor that binds to DNA to trigger transcription of genes involved in cell cycle inhibition. (high levels of p53 proteins indicate that DNA is damaged)
p53 protein prevents cancer by:
- activating DNA repair proteins when DNA has sustained damage ⮕ ensures damaged DNA is not replicated
- arresting growth by holding the cell cycle at the G1/S regulation point upon DNA damage recognition ⮕ ensures damaged DNA is not replicated and gives time for the cell to repair DNA damage. [activated p53 protein binds to specific DNA control elements & promotes transcription for relevant genes like p21, which stops the cell cycle by binding to proteins involved in cell cycle progression like Cdks]
- initiating apoptosis when DNA damage proves to be irreparable. [p53 protein activates ‘suicide’ genes that ensure cells with damaged DNA does not continue to proliferate
loss of function mutation to both copies of p53 gene = defective/missing p53 protein = unable to inhibit cell cycle when DNA is damaged = cells containing damaged DNA proliferate indefinitely (UH-OH!!)
what is the function of a proto-oncogene?
proto-oncogenes code for gene products that promote normal cell division.
proto-oncogene products include:
1. growth factors that stimulate cells to divide
2. growth factor receptors, membrane proteins that bind to growth factors
3. protein kinases that phosphorylate & thus activate proteins
4. inhibitors of apoptosis, which reduces rate of cell death
5. transcription factors which control rate of transcription
what kind of mutation ?
under what circumstances will defective proto-oncogene products be formed?
a gain in function mutation must occur.
a mutation of one of the two copies of a proto-oncogene into an oncogene is sufficient to cause abnormal cell proliferation. the oncogene acts in a dominant manner (since only 1 copy needs to be mutated). this is a gain in function mutation, leading to genes to gain function, eg being over-expressed or coding for hyperactive proteins which lead to uncontrolled cell division