Growth Control (14) Flashcards
What are the three main factors that control growth?
1- Cell lineage
2- External/ Diffusible Factors
3- Cell-cell/ Cell- ECM interactions
What is cell lineage?
Internal control of G1/S transition
When does apoptosis occur?
During normal development and also in adulthood
Why does apoptosis occur?
It is usually a result of checkpoint error during DNA replication/ cell cycle
What are three examples of apoptosis during normal development?
1- Formation of the digits
2- Epithelial cells during palate fusion
3- Neurons in developing brain
Name two examples of apoptosis that occurs in normal adult cells?
1- Lining of the gut
2- Mammary tissue post-lactation (due to hormone deprivation)
What is the fol of apoptosis during the development of the brain?
To control the number of neuros. Cell death matches the number of nerve cells to number of target cells.
Trophic signals are required for cell survival.
Describe the morphology that an apoptotic cells?
They shrink, then form membrane blebs and then fragment, releasing small membrane-bound apoptotic bodies that are phagocytosed by macrophages
What happens to necrotic cells?
They swell and burst
Which cells are usually associated with inflammation….Necrotic cells or apoptotic cells?
Necrotic cells
What is Bad allowed to do when there are no trophic factors present?
Bad can interact with the anti-apoptotic proteins….Bcl2 and Bclxl
Where are Bcl2 and Bclxl located?
Outer mitochondrial membrane
What does the interaction of Bad with Bcl2 and Bclxl inhibit?
The interaction of Bcl2 and Bclxl with Bax is inhibited?
What happens when the Bax is not inhibited?
Bax containing ion channels form and the release of cytochrome C from the mitochondria into the cytosol. This results in the activation of a series of cysteine proteases called caspases.
What is the action of caspases?
They digest important intracellular structural proteins such as the nuclear lamins and cytoskeletal proteins leading to the cells demise and fragmentation
What is terminal differentiation?
Cell stops dividing and express a novel set of genes for specialized function
What is senescence?
Ceasing cell division due to absence of telomerase
What is telomerase?
A ribozyme (part protein, part RNA)
It adds a 6 base repeat to parental DNA strand and permits the completion of synthesis of the lagging strand
True or False: Most adult somatic cells have telomerase.
False….most lack telomerase
How is senescence activated?
When telomeres get too short, p53 is activated and then this activates p21 CDK inhibitor
What is the function of p21 CDK inhibitor?
It blocks the cell in G1t
Give an example of a growth factor that acts locally
Platelet derived growth factor is released from activated platelets and this stimulates wound repair
Give an example of a growth factor that works systemically?
Erythropoietin which is synthesized in the kidney…this stimulates RBC differentiation in bone marrow
What is the importance of anchorage- dependent cell growth?
It provides cell surivial signals to preventapoptosis
What is contact inhibition?
Cell-density dependent growth inhibition (when the cells touch they stop growing)
Nerve and cardiac muscle cells are examples of _______ cells.
Permanent cells
If cells regenerate, what do they regenerate from?
Undifferentiated stem cells. They replace differentiated cells that cannot divide
Describe the organization of the skin epidermis is maintained?
1- Stem cells attached to basal lamina continue to divide as long as the cells are anchoraged
2- Decrease in integrins/ Focal adhesions/ hemi-desmosomes
3- Detached cells stop proliferation and this drives differentiation
4- Increased caderins/keratins/ desmosomes
5- Provides strength/ barrier characteristics of skin
6- Cells die/ flatten but continue to function as barrier
7- Sloughed off and replaced
Growth control is a balance of _______ and _________ signals.
Stimulatory and inhibitory
What is different in transformed cancer cells?
Do not senesce
Lack growth factor dependence
Lack anchorage dependence
No cell-cell contact inhibition
What are the two main classes of mutation that affect the function of proteins involved in growth regulatory signal transduction pathways?
Oncogenes and tumor suppressor genes
What are oncogenes?
Mutated or overexpressed versions of genes normally found in cellular genomes
What where the first discovered oncogenes?
Viral oncogenes in retroviruses
Generally, what are the functions of proto-oncogenes?
They are proteins that normally stimulate growth/ cell proliferation
2- Conversion to an oncogene result in
True or False: Mutation of a single allele of a proto-oncogene can cause abnormal growth.
True
What is the normal function of tumor suppressor genes?
Normally function to oppose the activity of proto-oncogenes…they normally inhibit growth
How many alleles of a tumor suppressor gene must be mutated or deleted before uncontrolled growth occurs?
Both alleles
True or False: First mutation/ deletion of Tumor suppressor genes is often inherited- individuals are predisposed to developing cancer.
True
What is retinoblastoma (Rb)? What happens when it is lost?
A negative regulator of gene transcription.
When it is lost there us unregulated transcription
What are the functions of p53?
Induces synthesis of a G1, CDK inhibitor (p21)
Blocks Rb phosphorylation
May induce apoptosis/ senescence
What does HPV produce that inhibits Rb and p53?
E6= Rb
E7= p53
What does SV40 virus produce that bind Rb and p53?
Large T antigen
What are the general stages of cancer progression?
Loss of cell division/ growth control
Ability to invade and metastasize
