Cancer

cancer

diseases of unregulated cell proliferation

malignant

tumor consisting of cells that invade other tissues

metastasis

movement of cells that separate from malignant tumors to other sites where they establish secondary tumors

genetic theory of cancer

some cancers are consistently associated with a particular chromosome abnormality and may run in families

Knudson model

cancer is a multistep process that requires multiple mutations in the same cell

“double hit hypothesis”

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one mutation does not guarantee it will develop into cancer

clonal evolution

mutations that enhance the ability of cells to proliferate predominantly in a clone of cells

oncogenes

mutated, dominant-acting, stimulatory genes (protooncogenes) that cause cancer

tumor suppressor gene

mutated, recessive-acting, inhibitory games that are inactive

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eventually leads to loss of heterozygosity

haploinsufficiency

mutant phenotype in an individual cell or organism that is heterozygous for a normally recessive trait

cyclin dependent kinase

combines with cyclin to phosphorylate (activate/deactivate) proteins

G1 to S transition

1\. RB protein binds to transcription factor

2\. cyclins increase in concentration and combine with CDKs (E2F)

3\. RB phosphorylated by CDKs

4\. transcription factor released and binds to promoter

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mutations in CDK, RB, cyclins etc. can lead to cancer (unregulated cell growth)

G2 to M transition

1\. cyclin binds with CDK to create inactive MPF

2\. MPF activated by dephosphorylation

3\. MPF increases until it reaches critical level

4\. MPF phosphorylates proteins for mitosis

5\. MPF decreases, initiating anaphase

receptor components

extracellular domain

transmembrane domain

intra cellular domain

drivers

mutation that directly contributes to the development of cancer

passengers

mutations that arise randomly in the process of tumor development and do not contribute to cancer progression

development of colorectal cancer

1\. APC gene mutation resulting in adenomatous polyp formation

2\. mutation in Ras gene in larger, more advanced polyps

3\. malignant cells have mutation in p53 gene leading to higher mutation rates