Topic 10: Cancer 3 Flashcards
what is the function of a tumor suppressing gene
they help prevent the formation of cancer by slowing down cell division or telling cells to die at the right time
how does retinoblastoma occur?
hereditary
- offsprings inherit one mutant Rb gene and occasionally the normal one gets inactivated then causes cell proliferation
non hereditary
- parent is normal but offpring randomly inactivates one of its 2 normal genes then in their offspring hereditary occurs
what types of mutations affect the tumour suppressor genes
- nondisjunction
- normal chromosome lost then mutated one duplicated
- mitotic recombination
- gene conversion (uses mutated gene as template)
- deletion of normal
- point mutation in normal
what does epigenetics mean?
it is the process that affects the expression of specific genes that the daughter cells inherit but don’t change the DNA sequence
what are the 2 epigenetic changes that can lead to loss of gene function
- high amounts of heterochromatin: a condensed form of interphase chromatin that silences genes making them transcriptionally inactive
- methylation of C nulceotides in gene promoters causes chromasome condensation and transcriptional repression
what are the 5 main classes of proteins coded by the turner suppressor genes and examples
- protien in signalling pathways that normally prohibit growth (TBF beta)
- proteins that normally regulate or inhibit progression through the cell cycle (Rb)
- checkpoint control proteins that arrest the cell cycle in response to DNA damage (p53)
- protien that promote apoptosis (pro apoptotic Bcl-2 proteins)
- enzymes that participate in DNA repair (BRCA1)
what are some examples of inherited mutation in other tumor suppressor genes
- BRCA-1: involved in repairing radon induced DNA damage
- APC: a component of Wnt signalling
what happens when p53 is mutated
since it is a transcriptional regulator it usually induces
- cell cycle arrest
- senescence
- apoptosis
if mutated, non of these things will occur, this mutation is present in 50% of all cancers
what is the difference between a driver and passenger mutation
a driver mutation is one that is commonly mutated in cancer (tall) the passengers usually are mutated after the drivers
what is TGF beta and what does it do?
it is transforming growth factor Beta and it prevents proliferation of mammalian cells by inducing synthesis of inhibitory proteins in the cell cycle
explain the mechanism of the TGF beta signalling
1) a TGF beta ligand will bind to type 2 and 1 TGF beta recptors
2) The type 2 will phosphorylate type 1 with its serine/threonine kinase
3) that allows type 1 to bind and phosphorylate Smad2 or 3
4) then smad2 or 3 dissociates and forms a complex with smad 4 (now called co smad)
5) then that co smad then translocates to the nucleus and regulates gene transcription
describe the consequences of loss of the TGF beta signalling
- the cell cycle will not be inhibited because p15 can not be induced
- the protease will not be inhibited and will digest the ECM
