19.3

Describe the relationship between proto-oncogenes and oncogenes. Explain how mutations in proto-oncogenes like p53 and the Ras gene can lead to cancer in humans

The genetic changes that convert proto-oncogenes to oncogenes are movement of DNA within a genome, amplification of a proto-oncogene, and point mutations in the control element or in the proto-oncogene itself. Cancer cells usually contain chromosomes that have broken and rejoined incorrectly, translocating fragments from one chromosome to another. If a translocated proto-oncogene ends up near a very active promoter or other control element, its transcription increases, making it an oncogene. Movement of transposable elements may place a very active promoter near a proto-oncogene, increasing its expression. Amplification increases the number of copies of the proto-oncogene. Point mutations can occur in the promoter or enhancer that controls the proto-oncogene, increasing its expression. Point mutations can also occur in the coding sequence, changing the gene's product to a protein that is more active or more resistant to destruction than a normal protein. The Ras gene is apart of the cell cycle stimulating pathway, which produces a protein that stimulates the cell cycle. This pathway is triggered by a growth factor that binds to its receptor in the plasma membrane. The signal is then relayed to Ras. Ras passes the signal to a series of protein kinases. The last kinase activates a transcription activator that turns on genes to stimulate the cell cycle. If a mutation makes Ras or any other pathway component abnormally active, excessive cell division and cancer will occur. The p53 gene is a part of the cell cycle inhibiting pathway, which produces a protein that inhibits the cell cycle. DNA damage is an intracellular signal that is passed by protein kinases to activate p53. Activated p53 promotes transcription of the gene for a protein that inhibits the cell cycle. Inhibition of the cell cycle ensures that the damaged DNA is not replicated. Mutations causing deficiencies in any pathway components can cause cancer.

explain how the types of mutations that lead to cancer are different for a proto-oncogene and a tumor suppressor gene

a cancer causing mutation in a proto-oncogene usually makes the gene product overactive whereas a cancer causing mutation in a tumor suppressor gene usually makes the gene product nonfunctional

define oncogenes

a gene found in viruses or as part of the normal genome that is involved in triggering cancerous characteristics

define ras gene

a gene that codes for ras protein a g protein that relays a growth signal from a growth factor or receptor on the plasma membrane to a cascade of protein kinases that ultimately results in the stimulation of the cell cycle. many ras oncogenes have a point mutation that leads to a hyperactive version of the ras protein that can lead to excessive cell division

define tumor suppressor genes

a gene whose protein products inhibit cell division thereby preventing uncontrolled cell growth, cancer

define proto-oncogenes

a normal cellular gene corresponding to a oncogene; a gene with potential to cause cancer but that requires some alteration to become an oncogene

define p53 gene

the guardian angel of the genome a gene that is expressed when a cell's DNA is damaged. its product p53 protein functions as a transcription factor for several genes

compare the usual functions of proteins encoded by proto-oncogenes with those encoded by tumor suppressor genes

the protein product of a proto-oncogene is usually involved in a pathway that stimulates cell division. the protein product of a tumor suppressor gene is usually involved in a pathway that inhibits cell division

under what circumstances do we consider cancer to have a hereditary component

when an individual has inherited an oncogene or a mutant allele of a tumor suppressor gene