Molecular Basis Of Cancer Flashcards
Initiation
Irreversible alteration of single, normal cell
(Starts acting weird)
Promotion
Potentially reversible clonal expansion of initiated cell
(Makes surrounding cells weird)
Progression
Conversion of initiated cell -> metastasizing cancer cell
(Weird tumor forms)
Example of a known promoter
Croton oil
Repeated exposure to tumor promoters causes
Tumor formation
4 main fates of promoted cells
- progress to lesion w/ higher neoplastic capacity
- grow w/o qualitative changes
- persist for long time w/o or w/ minimal growth & w/o qualitative changes
- regress completely
6 hallmarks of cancer
- self sufficient growth signals
- don’t respond to growth inhibitors
- evasion of apoptosis
- uncontrollable growth (limitless)
- sustained angiogenesis
- metastasis and tissue invasion
Cancer etiopathogenesis caused by alteration of
- proto-oncogenes
- tumor suppressor genes
- apoptosis genes
- DNA repair genes
Main 2 cencer etiopathologies
- proto-oncogenes
- tumor suppressor genes
List some Proto-oncogenes
- tyrosine kinases
- G proteins
- DNA binding proteins
- signal transducers
Proto-oncogenes
- encode for oncoproteins
- normal cell genes that regulate cell growth & diff.
Oncogenes
- altered proto-oncogene that promotes abnormal cell growth
- promote autonomous cell growth in cancerous cells
Most commonly mutated oncogenes
In ras family
Proto-oncogene alterations
- point mutation
- gene amplification
- translocation
Common tumor suppressor gene
P53
Tumor suppressor genes
- transcribed protein regulates growth
- inactive form confers growth advantage
BAX
Apoptosis gene
P21
CDK Inhibitor
GADD45
DNA repair
BCL-2 family
Anti-apoptosis genes
DNA Repair genes
- influence non-lethal damage repair in other genes
- dsyfunction-> genomic mutations
- ex. GADD45, MLH1, MSH2
Environmental causes of cancer
- chemical carcinogen
- radiant energy
- oncogenic viruses
Chemical carcinogens
- synthetic or biological
- 2 classes: direct-acting or procarcinogens
- most are mutagens
- highly reactive electrophiles that form DNA adducts
Direct acting carcinogens
Don’t need to be metabolized
Procarcinogens
Require chemical or enzymatic activation
Radiant energy carcinogens
- are complete carcinogens (initiate & promote)
- direct DNA damage
- reactive O2 spp indirectly damages DNA
Types of cancers assc. w/ radiation
- melanomas
- squamous cell carcinoma
- basal cell carcinoma
- leukemia
- thyroid cancer
- breast cancer
DNA Oncogenic virus
- transforming DNA viruses form stable assc. w/ host genome
- productive infection
- non productive infection
Productive infection
- permissive cells
- virus replication occurs
- frequently cytotoxic
- not assc. w/ tumor form. usually
Non-productive infection
- non permissive cells
- virus can’t replicate
- can cause cell transformation and tumor formation
DNA Oncogenic virus steps of infection
- virus enters cell
- viral envelope removed
- v-DNA incorporated in host genome
- synth. Of viral proteins
- replication of genes that encode viral capsid proteins
- infectious virions produced
Additional virion production w/ cell lysis doesn’t occur in
Non permissive cells
DNA papova viruses
Papilloma, polyoma, simian virus 40
Adenoviruses are DNA
True
DNA Herpesviruses
Marek’s, reticulum cell sarcoma in monkeys
RNA oncogenic viruses
- retroviruses & oncornaviruses
- have RNA dependent DNA polymerase or reverse transcriptase
- makes DNA copies of itself w/ RNA
RNA Oncogenic oncornaviruses
FeLV, Mouse mammary tumor virus, jaagsiekte virus type D
