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43 Cards in this Set
- Front
- Back
Cencer cells share two fundamental properties:
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- unregulated cell proliferation
- metastatic spread |
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genomic alteration associated with cancer:
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- single-nucleotide substitutions
- large scale chromosomal rearrangements - amplifications - deletions |
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clonal
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tumors originated from a common ancestral cel that accumulated numerous specific mutations
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SLIDE 8
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do this one!
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tumorigenesis
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each step is the result of one or more genetic alterations that progressively release the cell from the normal controls on cell growth and proliferation.
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mutator phenotype
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high level of genomic instability in cancer cells
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cancer cells show higher than normal rates of :
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- mutation
- chromosomal abnormalities - genomc instability |
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genomic instability can cause:
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- translocations
- aneuploidy - chromosome loss - DNA amplification - chromosomal deletions |
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Epigenetics
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the study of factors that cause DNA modifications in a heritable way without affecting he nucleotide sequence of the DNA.
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G0
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cells that stop proliferating enter this stage in which they do not grow or divide but are metabolically active.
CANCER CELL ARE UNABLE TO ENTER G0 |
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Signal Transduction
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initiates a program of gene expression that propels the cell out of G0 and back into the cell cycle.
CANCER CELLS OFTEN HAVE DEFECTS IN SIGNAL TRANSDUCTION PATHWAYS |
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G1/S, G2/M, and M checkpoints
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this is where cells decide whether to proceed to the next stage of the cell cycle.
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Cyclins
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mediates regulation of cell cycle
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Cyclin-dependent Kinases (CDKs)
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regulate synthesis and destruction of cyclin proteins
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Cells halt progress through the cell cycle if ______ are abberant/
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DNA replication, repair, or chromosome assembly
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apoptosis
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programmed cell death; if DNA damage is so sever that repair is impossible the cell may initiate this.
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caspases
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a series of proteases responsible for initiating apoptosis and for digesting intracellular components
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Bcl2-BAX
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heterodimer thta joins together the homodimers Bcl2 and BAX and is an active complex
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Bcl2 homodimer
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blocks apoptosis
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BAX
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promotes apoptosis
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Proto-oncogenes
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genes whose products promote cell growth and division
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Proto-oncogenes encode:
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- transcription factors that stimulate expression of other genes
- signal transduction molecules that stimulate cell division - cell-cycle regulators that move through the cell cycle |
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In cancer cells one or more proto-oncogenes...
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are altered in such a way that their activities cannot be controlled normally.
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oncogene
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a proto-oncogene that i mutated or aberrantly expressed and contributes to the development of cancer.
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tumor suppressor genes
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normally regulate cell cycle checkpoints and initiate the process of apoptosis.
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when tumor suppressor genes are mutated or inactivated
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cells are unable to undergo apoptosis if DNA damage is extensive.
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ras genes
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encode signal transduction molecules that regulate cell growth division.
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Mutations that convert the ras proto-oncogene to an oncogene...
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freeze the ras protein into its active conformation, constantly stimulating the cell to divide.
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Cyclins
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form complexes with CDKs that are importnat regulators of each phase of the cell
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Cyclin D1 and Cyclin E are...
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proto-oncogenes
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p53 tumor suppressor gne
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encodes a nuclear protein that acts as a transcription factor that represses or stimulates transcription of more than 50 different genes.
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cells lacking p53
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are unable to arrest the cell cycle at checkpoints or enter apoptosis in response to DNA damage.
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RB1 tumor supressor gene
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contributes to the development of many cancers due to unregulated progression through the cell cycle
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familial retinoblastoma
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a mutated RB1 is inherited
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Sporadic retinoblastoma
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requires two independent mutational events of RB1 within the same cell
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retinblastoma protein
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a tumor supressor protein that controls the G1/S cell cycle checkpoint.
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metastasize
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the primary tumor cells must digest components of the extracellular matrix and basal lamina that normally inhibit migration of cells.
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proteolytic enzymes
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present at higher than normal levels in highly malignant tumors and are not susceptible to the normal controls conferred by regulatory molecules.
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familial adenomatous polyposis
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an example of the necessity of mutation in other genes to fully express the cancer phenotype.
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Most animal viruses that casue cancer are
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retroviruses.
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acute transforming retroviruses
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viruses that cause cancer in animals because they transform normal cells into cancer cells
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carcinogenic
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any substance or event that damages DNA causing mutations to occur in proto-oncogenes or tumor suppressor genes
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carcinogens can be:
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chemicals, radiation, some viruses, and chronic infections
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