What are the 7 hallmarks of cancer
- Self sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Ability to invade and metastasize
- Evasion of host immune response
What is the difference between a proto-oncogene and an oncogene?
- Proto-oncogenes encode proteins that normally stimulate cell proliferation
- Oncogenes are altered forms of proto-oncogenes; sustained gain of function alterations resulting from changes in the genome. Accelerated proliferation causing unregulated cell growth (ie- mutated gene coding for GF, signaling enzymes, or transcription factors)
How can oncogenes affect GF’s?
-Overexpression of autocrine GF (meaning they act on oneself= self sufficiency in growth)
Overexpression (several receptors on cell so any GF in vicinity can activate)
-Constitutive activity (GF receptor stays on and is activated by all circulating GFs)
How can oncogenes affect signal transducing proteins?
-Cytoplasmic signaling (keeps cell’s enzymes active) and Nuclear transcription factors. This activates the cell cycle= proliferation.
What do tumor suppressor genes do?
Encode proteins that initiate DNA repair and inhibit cell proliferation or stimulate apoptosis. p53 and BRCA1 and 2 are TSG
What is the role of the tumor suppressor gene, p53?
1- To initiate DNA repair
2- Triggers apoptosis if DNA beyond repair
-They are also able to produce proteins that inhibit cellular division
Tumor suppressor genes are usually recessive, what does this functionally mean?
Two alleles must be altered to lose the TSG function. This is different than a proto-oncogone which needs only one mutation to become an oncogene.
Describe how cancer can affect the body with suppression of p53.
- A mutation inactivates the suppressor gene
- Cell proliferate
- Mutations inactive DNA repair genes
- Proto-oncogenes mutate to oncogenes.
- More mutations, more genetic instability which facilitates metastatic disease
Why is telomerase advantageous for cancer cells to possess?
Gives the cancer cells limitless replicative potential by protect the telomeres that naturally degrade/shorten with each cell division.
What happens during angiogenesis?
Once the tumor reaches a certain size it requires more oxygen and nutrients so it releases proteases which degrade the surrounding environment allowing the tumor to grow in size and create capillary blood vessels necessary to prevent hypoxia.
What are three ways cancer can evade the body’s immune response?
- Failure to produce tumor antigen (lack of T cell recognition of tumor)
- Mutations in MHC genes or genes needed for antigen processing (remove ability to be recognized-lack of T cell recognition of tumor)
- Production of immuno-suppressive proteins (release message to inhibit T cell activation)
What are the three main challenges in the treatment of cancer?
- Mechanisms of cell proliferation/destruction of normal cells.
- Heterogeneous disease
- Genetic instability of cancer cells (many are adaptive and acquire drug resistance)
Familial retinoblastoma involves the transmission of what from parent to offspring?
Mutant tumor suppressor gene
