Cancer Flashcards
Carcinomas
Cancers of epithelial cells
Colon, breast, lung
Sarcomas
Cancers of supporting tissue
Bone, muscle, cartilage, fat
Lymphomas/leukemias
Cancers of lymphatic or blood origin
Melanoma
Cancer of melanocytes
Skin, eye, intestines
Blastoma
Cancer originating in embryonic cells
Kidney, brain, retina
Affects children
4 common characteristics of cancer
- Uncontrolled proliferation (benign and malignant): unregulated cell division, immortal
- De-differentiated (benign and malignant): return to stem cell-like state
- Invasive (malignant): invade surrounding tissue, crowd out healthy cells
- Metastasize (malignant): able to pick up and move, evade immune system, and form secondary tumors elsewhere
Causes for uncontrolled growth
Telomerase activity Can grow in hypoxia (low oxygen) Ras, cyclin-Cdk malfunctions Avoidance of apoptosis DNA mutations
Causes for de-differentiation
Express stem cell genes
DNA mutations
Causes for invasion
Lack cadherins
Can grow in hypoxia
Lack integrins (anchor cell)
Metalloproteases (destroy cell connections)
Angiogenesis (make blood vessels that feed tumor)
DNA mutations
Causes for metastasis
Invade blood stream (get through basal lamina)
Express proteins that help evade immune system
Angiogenesis (make blood vessels that feed tumor)
DNA mutations
Differences between malignant and benign tumors
Malignant: large and misshapen nuclei, disorganized tissue, poorly differentiated, poorly defined tumor boundary, high rate of division
Benign: normal nuclei, normal tissue organization, well-organized tissue, well differentiated cells, well defined tumor boundary, low rate of division
How normal cell becomes cancerous
Genetic instability causes an accumulation of mutations
Accelerated growth (oncogenes)
Inhibition of cell death (mutated tumor suppressors)
Hallmarks of cancer found in karyotype
Aneuploidy (abnormal # of chromosomes)
Altered chromosomes: accumulation of DNA damage (cell cycle is going too fast- damage isn’t repaired)
Examples: translocation (chromosome breaks and is attached to another non-homologous chromosome), broken chromosomes, more chromosomes than normal
Causes of cancer
Radiation (excitation of water surrounding DNA- free radicals attach to DNA)
Carcinogens
Viruses (ex- HPV inserts its genome into your genome: Rb protein can’t hold back cell cycle)
Hormones
UV
Spontaneous mutations
Inherited mutations
Tumor formation
Progressive increase in number of mutations (usually requires more than one “hit”)
Continually unrepaired DNA damage: mutation gives one cell an advantage, second mutation increases advantage, third mutation increases advantage and makes cell invasive, and so on
Mutations in proto-oncogenes
Proto-oncogene is mutated into oncogene
Dominant mutation
Gain of function: protein product is doing something that it didn’t use to do
Single mutation event in proto-oncogene creates oncogene (only one copy of proto-oncogene needs to be mutated to change activity)
Ways that proto-oncogene can become oncogene
Mutation in coding sequence: introduction of amino acid that causes protein to be always active
Gene amplification: normal protein greatly overexpressed
Chromosome rearrangement: coding sequence of proto-oncogene is rearranged so that it winds up next to the promoter OR sequence is fused with promoter
Normal functions of proto-oncogene products
Activation of cell cycle (Ras, cyclins, receptors, kinases, transcription factors, etc.)
Inhibition of apoptosis (Bcl2)
Ras pathway
Ras is a proto-oncogene
- Signal molecule binds to RTK (receptor tyrosine kinase)
- RTK is activated
- RTK activates Ras-activating protein
- GDP is phosphorylated into GTP and binds to Ras protein, activating it
- Activated Ras protein binds to MAP (mitogen-activating protein) kinase kinase kinase
- MAP kinase kinase kinase hydrolyzes ATP and phosphorylates MAP kinase kinase, activating it
- MAP kinase kinase hydrolyzes ATP and phosphorylates MAP kinase, activating it
- MAP kinase hydrolyzes ATP and phosphorylates either a protein or a transcription factor, causing either changes in protein activity or gene expression
- Cell cycle activation
Mutations in tumor suppressor genes
Recessive mutation
Loss of function: lose protein activity
2 inactivating mutations needed to change tumor suppressor gene function: loss of heterozygosity
Normal functions of tumor suppressor gene products
Inhibition of cell cycle (p21, p53, Rb)
Initiation of apoptosis (BAX, caspases)
Activation of DNA repair
p53 pathway
p53 is a tumor suppressor gene
Mutate p53: no p21 -> rapid progression of cell cycle
DNA damage activates protein kinases that activate p53 protein -> active p53 binds to regulatory region of p21 gene -> transcription and then translation of p21 gene -> p21 protein binds to cyclin-Cdk complex, inhibiting it
Rb pathway
Rb is a tumor suppressor gene
Mutation of Rb: Rb can’t hold transcription factor -> unregulated cell growth
Mitogen binds to mitogen receptor in cell membrane -> mitogen-activated protein (MAP) kinase cascade -> activation of Cdk -> Rb protein is phosphorylated -> Rb lets go of transcription factor -> cell proliferation
Role of inheritance in tumor suppressor genes
Inheriting a mutation in a tumor suppressor gene increases the likelihood of cancer
