Oncology 3- Tumourigenesis Flashcards
Protooncogenes
-normal genes that enhance cell growth, proliferation, function and inhibit apoptosis
>includes growth factors, growth factor receptors, signal transducers, apoptosis regulators
Oncogenes
-mutated form of gene
-a dominant change (so only one gene needs to be affected) resulting in increased cell replication and inhibition of apoptosis
Oncogene mutation
-RAS-A is permanently turned on
>dephosphorylation does not occur and there is an continuous increase in cell replication
DNA damage
-many potential causes and very frequent
>there are multiple proofreading and repair enzymes
>BUT as there are progression through the cell cycle and DNA division with damaged DNA, this damage becomes “fixed”= permanent
Tumour suppressor genes
-normal cellular genes that inhibit cell proliferation and growth (FIX it or DIE)
>includes cell adhesion molecules, ell cycle regulatory molecules, signal transducers, growth inhibitory factors
Ex. p53, and Retinoblastoma genes
P53
-located in 2 locations within the cell replication cycle that check for DNA damage =guardian of genome
-stimulated by many signals (cell in harmful damage, stressors)
P53 biologic effects
1.prevents cells from progressing through cell cycle
2.activates genes that help with cell repair
3.activates cells that induce apoptosis
Retinoblastoma gene (RB)
-acts like a boot on a car. Will prevent DNA from uncoiling and therefore cannot replicate
Tumour suppressor genes affected by mutation
-One hit: germ cell mutation
>predisposed to damage because already partially damaged by only having one good allele
-Two hits: somatic cell mutation
>have to be unlucky and have both alleles damaged
**Both alleles need to be affected because it is recessive
Epigenetic change
-heritable change in gene expression without DNA sequence alteration
DNA methylation
-addition of methyl groups to DNA in specialized islands which physically prevents transcription of the gene
>decrease methylation=increase transcription of gene
>increase methylation= gene slicing
Imprinting
-normal suppression of maternal or paternal allele of gene in a somatic cell
Loss of imprinting
-results from a DNA methylation
-results in both the maternal and paternal allele being expressed, resulting in increased levels of growth factors being produced
MicroRNA
-genes that encode short strands that bind to complementary mRNA and prevent protein translation
>another form of gene expression regulation and can act as an oncogene or a tumour suppressor gene depending on target mRNA
Malignant transformation criteria
**will most likely have all of these
1.Mutated DNA repair genes
2. Mutated oncogenes
3.Mutated or no tumour suppressor genes