Exam 4: Cancer Flashcards
(54 cards)
Epigenetic changes
process that alters gene activity without changing DNA sequence and leads to modifications that can be transmitted to the cell’s progeny - can lead to cancer
proto-oncogene
gene associated with control of cell division, act to promote cell growth
Oncogene
mutated proto-oncogene
excessively active in growth promotion - enhanced gene expression, production of hyperactive protein product, etc.
preserves activity of protein but results in excessive protein production or disrupts normal control of function
typically dominant mutation
Tumor suppressor genes
normally function to inhibit cell growth and division
mutations that inactivate tumor suppressor genes allow for inappropriate cell division
Caretaker genes
protect integrity of genome
ie DNA repair enzymes
when inactivated by mutation cells accumulate damaged DNA at a higher rate
Metastatic cancer
cancer that spreads to other parts of body
6 capabilities that cell must acquire to be transformed into invasive tumor
Self-sufficiency in growth signals Insensitivity to antigrowth signals Evading apoptosis Limitless replicative potential Sustained angiogenesis Tissue invasion and metastasis
Self-sufficiency in growth signals
oncogene products act to send inappropriate growth signals
Insensitivity to antigrowth signals
Loss of tumor suppressor fuction leads to loss of sensitivity to antigrowth signal
Evading apoptosis
needs to block cell death to become cancerous
mutations of components of pathway that lead to apoptosis
Limitless replicative potential
need to not senescence - which limits replication
Reactivates telomerase to lead to unlimited cell division potential
Sustained angiogenesis
cells achieve ability to promote and sustain angiogenesis (growth of blood vessels) to deliver oxygen and nutrients to tumor
Tissue invasion and metastasis
changes in expression of cell surface molecules leads to ability to migrate & invade nearby tissues
increase in expression of proteases that degrade extracellular matrix
dominant mutation
only one allele needs to be mutated for effect to be seen
i.e. gain of function like oncogenic
ErbB1/HER 1
receptor for epidermal growth factor (EGF), tyrosine kinase
activates MAP kinase cascade & cell growth/proliferation
proto-oncogene - mutation converts to consitutively active forms
ErbB1 constitutively active mutation
truncates protein & removes extracellular binding domain - activation of kinase domain
signal to grow delivered in absence of appropriate stimulus
HER2 constitutively active mutation
point mutation allows receptor dimerization and autophosphorylation in absence of ligand
Overexpression of HER2 protein seen in
many breast cancers
Overabundance of receptors allows cell to respond to very low concentrations of EGF = active more often
Ras constitutively active mutation
dominant mutations that favor GTP binding
Ras turned on without ligand binding
Very common in human cancers, especially pancreas & intestinal
c-Fos and c-Myc
transcription factors that activate genes needed for cell cycle progression (cyclins)
mutations stabilize mRNA/encoded protein, stays longer, inappropriate activation of growth promoting genes
Burkitt’s lymphoma
caused by inappropriate Myc activity
translocation moves c-myc gene from chromosome 8 to chromosome 14
myc gene now continually expressed (close to new promotor regions) and B-cell becomes cancerous
recessive mutation
damage to both alleles of gene required to give rise to unregulated cell proliferation
typically found in tumor suppressor genes
two hit model
same gene in same cell needs to get both alleles mutated for affect to be seen - somatic mutation - more rare
Retinoblastoma
Hereditary: inherit one mutated copy of RB1 gene, second somatic mutation results in retinal cell with no functional Rb protein = tumor formation more likely because lack of inhibition of cell division cyclins
Tumors develop in both eyes
Sporadic: two separate mutations required in cell
