Neoplasia Flashcards
Neoplasia
Growth of genetically altered cells. Can have no significance or fatal
Causes of neoplastic cells
-Inherited
-Chemicals
-Infectious agents
-Physical agents
Inherited neoplasia
Germline DNA abnormalities are passed from generations Can cause neoplasia or predisposition of neoplasia
Chemical exposure neoplasia
Endogenous or exogenous chemicals act as mutagens or carcinogens
Infectious agent neoplasia
Viruses notable cause, Incorporate or activate oncogenes or suppress host responses against neoplastic cells
Physical agents neoplasia
Radiation with short wavelengths damage DNA (UV, X rays, gamma rays)
DNA damage checkpoints
-G1/S
-S
-G2/M
arrest if damage present
DNA replication checkpoint
G2/M. Arrest until replication is complete
Spindle checkpoint
M stage. Makes sure chromosomes aligned
Morphogenesis checkpoint
G2/M. Arrest when cytoskeletal abnormalities
Protooncogenes
Promote cell growth and division
Tumor suppressor genes
Inhibit cell growth and division
What genes are commonly associated with cell transfromation
-Protooncogenes
-Tumor suppressor genes
-Regulate DNA repair
-Regulate apoptosis
Protooncogene examples
-hst and erb genes (growth factors)
-ras gene (signal transducer)
-myc gene, cyclinds and CDK (regulators of the cell cycle)
Ways protooncogenes become oncogenes
-Damage to coding sequence and get abnormal protein(oncoprotein)
-Damage from outside of the coding region but dysregulate expression
Oncoproteins
No regulatory controls tend to push cell cycle faster and see increased number of abnormal cells
Mutated RAS
Lead to permanent activation of pathway even without external signals. Lots of transcription
Tumor suppressor gene examples
-Inhibitory cytokines
-Signal transducers and mediators (nf-1 and APC)
-Inhibitory regulators of the cell cycle (p53 and RB)
Tumor suppressor genes
Counteract protooncogenes
Mutated RB
Tumor suppressor. Blocks movement through the cycle normally. If phosphorylated it will no longer suppress RAS get too much transcription
Pathogenesis of tumor suppressor gene
-damage to coding region resulting in abnormal protein
-Damage in non coding region and get dysregulation of protein synthesis
Mechanism of mutation to DNA repair genes
-exposure to mutagens
-Mistakes during DNA replication
DNA repair genes
Many mistakes are made so mutations are common and are often just fixed. Able to repair because it has two strand and you have a template
BRCA1
Repair double stranded breaks. Mutations in this lead to neoplasia due to DNA mutations in dividing cells go up. Can be congenital or acquired
Apoptotic genes
Prevent cells with unrepaired DNA damage from replicating. Many are also protooncogenes and tumor suppressor genes. Consist of Bcl-2 gene family
Apoptotic gene examples
-p53 uses p21 to cause cell cycle arrest if not repaired it causes apoptosis.
Mitochondria and apoptosis
Houses important stimulants for apoptosis. If it gets leaky it releases cytochrome C which sets of the caspases causing apoptosis
Transformed cells
Unstable and can lead to more acquired mutations. Sequence of mutations will determine whether it develops into neoplasia. Loos at the pattern
Feline mammary carcinoma
HER2
Canine mast cells tumors
Kit mutations
Canine mammary neoplasia
BRACA 2
Bovine leukemia virus associated lymphosarcoma
p53 overexpression
p53 and RAS mutations
More common in humans than it is in dogs and cats
Other causes of neoplasia
-Non mutagenic stimuli (food etc) alter cell cycle events. Don’t alter DNA
-Epigenetic heritable changes. Doesn’t change DNA may be post-translational
