Biochemistry 2280A Chapter Notes - Chapter 20: Antibody, Knockout Mouse, Catenin

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Biochemistry 2280 – Topic 24 – Molecular Basis of Cancer
Textbook Notes
Ch. 20 – Cell Communities: Tissues, Stem Cells, and Cancer
Pg. 702 - 725
Tissue Maintenance and Renewal
TISSUES ARE ORGANIZED MIXTURES OF MANY CELL TYPES
Most tissues have blood vessels lined with endothelial cells, Schwann cells around
axons, macrophages for clean-up, etc.
How tissue organization is maintained
oCell communication
Each type of specialized cell looks out for signals, acts accordingly
Ensures new cells produced only when required
oSelective cell adhesion
Cells stick selectively according to hemophilic binding (binding between
same type of cells)
Cells also form selective attachments to other cell types and extracellular
matrix components
This prevents cells in tissue from getting jumped
oCell memory
Gene expression patterns established during embryonic development
maintained throughout – i.e. fibroblasts only produce more fibroblasts
DIFFERENT TISSUES RENEWED AT DIFFERENT RATES
Cell turnover varies
oEx. Most nerve cells last lifetime, intestinal epithelium renewed 3-6 days
Radiation can disrupt renewal cycle
STEM CELLS GENERATE CONTINUOUS SUPPLY OF TERMINALL DIFFERENTIATED
CELLS
Terminally differentiated: cells that cannot divide, at end of developmental pathway
oEx. Red blood cells cannot produce more red blood cells
Differentiated cells come from precursor cells, which are derived from self-renewing
stem cells
When stem cell divides, daughter cells has choice – become stem cell or head along
differentiation pathway
Stem cells are in small numbers and difficult to identify
oEach tissue has them
Ex. Stem cells in epidermis
oFound at basal layer above dermis
oDifferentiated cells rise up, eventually shed at topmost layer
Often, single stem cell can produce many cell types
oEx. Hemopoietic stem cell produces red blood cells and many types of white
blood cells in bone marrow
SPECIFIC SIGNALS MAINTAIN STEM-CELL POPULATIONS
Ex. Wnt proteins promote proliferation of stem cells and precursor cells at base of each
small intestinal crypt
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oCells there also produce signals to limit Wnt pathway from affecting cells outside
crypt
oOther signals determine what kind of cell is produced from differentiation
oDefects in Wnt regulation can lead to intestinal cancer
STEM CELLS CAN BE USED TO REPAIR LOST OR DAMAGED TISSUES
Ex. Bone marrow transplant in leukemia patients restores lost red blood cells
Embryonic stems cells are pluripotent – can give rise to all tissues and cells (including
germ cells) if put back into early embryo
oMost useful, can differentiate into anything
oEx. Can restore degenerative muscle fibers in patients with muscular dystrophy,
or insulin-secreting cells in diabetes I patients
Problem with ES cells – rejection by immune system
THERAPEUTIC CLONING AND REPRODUCTIVE CLONING ARE VERY DIFFERENT
Reproductive cloning via nuclear transplantation
oNucleus of unfertilized egg cell removed, replaced with diploid cell from organism
to be cloned
oHybrid cell grows into 200 cell blastocyst
oBlastocyst transferred into foster mother – clone born
Therapeutic cloning produces ES cells rather than organism
oUsed to be grafted back to donor to minimize immune rejection
INDUCED PLURIPOTENT STEM CELLS PROVIDE CONVENIENT SOURCE OF HUMAN ES-
LIKE CELLS
No need for nuclear transplantation (very difficult process), can create ES-like cells with
transcription regulators Oct3, Oct4, Sox2, and Klf4
oThese cells are induced pluripotent stem cells (iPS), made directly from adult
tissue
oHowever, conversion rate from regular cell to iPS cells is low, and more research
needs to be done to ensure safety when treating human diseases
oRight now, iPS cells used for testing drugs, especially for rare conditions
Cancer
CANCER CELLS PROLIFERATE, INVADE, AND METASTASIZE
EPIDEMIOLOGICAL STUDIES IDENTIFY PREVENTABLE CAUSES OF CANCER
Ex. Vaccination against human papillomavirus decreases chance of cervical cancer
However, cancer is not infectious disease in general
Factors that increase risk of cancer
oObesity
oSmoking tobacco
CANCERS DEVELOP BY ACCUMULATION OF MUTATIONS
Spontaneous mutations can still occur without external risk factors
oBut have to affect right gene to be cancerous, also accumulate slowly over time
Cancer cells not only mutated but also genetically unstable
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