Radiation Oncology/Radiobiology/Growth Factors
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Growth Factors
ErbB
[edit | edit source]- Family of 4 receptor tyrosine kinases
- Transmembrane proteins, existing as monomers at surface
- When a ligand binds, dimerisation arm becomes untethered, and the proteins dimerize
- Tyrosine kinase activity
EGFR
[edit | edit source]
- Ligands:
- Epidermal growth factor (EGF): produced by platelets, macrophages, salivary glands, kidneys
- Transforming growth factor alpha (TGF-α): produced by macrophages, brain cells, keratinocytes
- HB-EGF, Amphiregulin, betacellulin, epigen, epiregulin: produced by various cells around the body
Review: PMID 15142631, Herbst R, IJROBP 2004
EGFR Pathways
[edit | edit source]- EGFR -> Ras -> Raf -> MEK -> MAPK -> myc -> transcription
- EGFR -> Ras -> Raf -> MEK -> MAPK -> RSK -> S6 -> transcription
- EGFR -> PI3K -> AKT -> mTOR
PTEN
[edit | edit source]- PTEN gene encodes a phosphatase, which uses PIP-3, which is also produced by PI3K above. Loss of PTEN therefore increases PIP-3 levels, leading to inappropriate AKT activity, and subsequent protection of cancer cells from apoptosis
- PTEN is a tumor suppressor
- PTEN loss confers resistance to EGFR inhibitors
- Please see PTEN Hamartoma Tumor Syndrome