ch 23 Flashcards
Palladin
encodes an essential component of a cell’s cytoskeleton; when
mutated, palladin contributes to the spread of pancreatic cancer
Why might this cancer rate differ between men and women?
Cancer is not a single disease; rather, it is a
heterogenous group of disorders characterized by
the presence of cells that do not respond to the
normal controls of cell division.
Normal cells in tumor formation
: grow, divide, mature, and die in response to internal and external signals.
Stimulatory and inhibitory signals regulate growth
Cancer cells in tumor formation
one or more of these signals has been disrupted.
Cell proliferates at an abnormally high rate.
Benign tumor
the tumor remains localized. A benign tumor is an abnormal (but noncancerous) collection of
cells
Malignant tumor
tumor cells invade other tissues.
Metastasis
the tumor cells induce secondary tumors
Alfred Knudson’s
- proposed cancer is the result of a multistep process that requires several mutations.
If one or more of the mutations
are inherited, fewer additional
mutations are required to
produce cancer, and the cancer
tends to “run in the family”.
“Two-Hit Hypothesis”
– only two mutations necessary
to cause the tumor.
Clonal Evolution
tumor cells accumulate
somatic mutations that
allow them to become
increasingly more
aggressive in their
proliferate properties.
Retrovirus
RNA virus that inserts a copy of its
genome into the DNA of a host cell that it invades,
changing the genome of that cell.
Retroviruses cause cancer by
- mutating and rearranging proto-oncogenes
− inserting strong promoters near proto-oncogenes - Human papilloma virus and cervical cancer
At least three types of
chromosome rearrangements with cancer
-deletions, inversions, and
translocations are associated
with certain types of cancer.
Epigenetic changes in cancer
Alterations to DNA methylation or chromatin structure are seen in many
cancers
Histone proteins are also often abnormally modified in cancer cells.
Hypomethylation
- an overall lower level of DNA methylation
− It is suspected that hypomethylation leads to activation of
oncogenes!
− Some evidence also suggest it causes chromosome instability –
a hallmark of many cancers.
Hypermethylation
- some specific CpG islands have extra methylation
− May deactivate tumor-suppressor genes
Two processes control the rate at which mutations
arise within a cell
1.The rate at which errors arise during and after
the course of DNA replication.
2.The efficiency with which these errors are
corrected.
Defects in genes that encode components of
DNA repair systems have been consistently
associated with a number of cancers.
13% of colorectal, endometrial, and stomach cancers have
cells that are defective in mismatch repair
DNA-repair system defects may also contribute to
chromosome rearrangements and genomic instability
Sequences that regulate the expression of the
telomerase gene are mutated in many tumor
cells.
This allows telomerase to be expressed and allows
cancer cells to divide indefinitely!
Many high risk neuroblastoma cancers in child
Oxygen and nutrients, essential to tumor survival,
are supplied by blood vessels, and the growth of new
blood vessels (angiogenesis) is important to tumor
progression
Angiogenesis is stimulated by growth factors and other
proteins encoded by genes whose expression is carefully regulated in normal cells.
In tumor cells, the genes encoding these proteins are
often overexpressed
Many tumor cells exhibit widespread
reduction in the expression of many miRNAs
Lower levels of miRNAs may contribute to
cancer by allowing oncogenes that are normally
controlled by miRNAs to be expressed at high
levels
Many cancers are caused by defects in this cell cycle
machinery!
– Mutations in the gene that encodes the RB protein are
associated with many cancers, including retinoblastoma.
– The gene that encodes cyclin D is overexpressed in
about 50% of all breast cancers.
– The tumor-suppressor gene p53 is mutated in about 75%
of all colon cancers
Oncogenes
mutated, dominant-acting,
stimulatory genes that cause cancer
– Proto-oncogenes: responsible for basic cellular
functions in normal cells; when mutated, they become oncogenes
driving transcription forward
Tumor-suppressor genes:
mutated recessive-acting inhibitory genes that are inactive
fixing the DNA
What causes the uncontrolled
cell growth?
1) Activation of Oncogenes
2) Inactivation of Tumor Suppressor Genes
Signal-transduction pathways
involve an external signal
triggering a cascade of intracellular reactions, producing a
specific response
Ras signal-transduction
pathway is activated when a
growth factor (such as epidermal
growth factor), binds to a
receptor on the cell membrane
Imagine you have a mutation in
this RAS gene.
The RAS proteins become
automatically activated and the cascade becomes almost continuous. What do you expect to happen to this cell?
This is an example of Oncogene Activation!
Too much gas pedal!
Mutations in genes encoding Ras
protein leads to cancer:
95% of tumors of the pancreas
45% of colorectal tumors
Cells have mechanisms to stop abnormal cells
from progressing through the cell cycle.
Tumor suppressor genes!
Role of environmental factors in cancer
