cancer

• evading apoptosis
• self-sufficiency 
• insensititvity to anti-growth signals
• sustained angiogenesis
• limitless replicative potential
• tissue invasion and metastasis

growth factors and their receptors: PDGF, FGF, EGF, CSF

Signal transducer:  ras, src, abl

Signal effectors: myc, fos, jun

mutated proto-oncogene

K-ras

leads to constitutive activation in the absence of growth factor stimulation

translocation of BCR-ABL

BCR on all the time and ABL need signal for proliferation

BCR-ABL specifically inhibitor target --> reduce signals

herceptin

amplification vs constant activation

•Recessive loss of function

Mutation in both copies required to have deleterious effect

•Mutation in one allele can be inherited in germline, causing inherited predisposition towards developing cancer

Mutation (genetic)

Methylation (epigenetic)

Deletion (loss of heterozygosity)

• point mutation: missense and nonsense
• Insertions: frameshifts
• Microdeletions

•DNA methylation- addition of methyl group, no change in DNA sequence (Epigenetic)

•Hypermethylation of CpG islands in gene promoters can lead to inactivation of the gene

Occurs in nearly every type of neoplasm

chromosomal deletion

chromosomal deletion

•Deletion

• ØNormal
• allele deleted (n=1)

Ø

•Uniparental Disomy (UPD)

ØNorma allele deleted

ØMutated allele duplicated (n=2)

•Inhibits cell cycle progression until cell is ready to divide

ØRb forms complex with E2F, preventing cell cycle progression from G1 to S

ØPhosphorylated Rb cannot bind E2F, allowing cell cycle progression

ØMutant Rb cannot bind E2F, allowing cell cycle progression

active p53 gene allow activation of cdk/cyclin complex 

inactivated p53 lead to cancer because can't repair DNA, apoptosis etc

familial just need loss of heterozygosity 

sporadic cancer required mutation and LOH

for tumors to progress, they must stimulate angiogenesis

activation of telomerase 

telomere gets shorter in normal cell --> cancer cell activate telomerase --> immortal cell

true