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43 Cards in this Set

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