Growth Control

Question 1

What are some examples of apoptosis during normal development?

Answer 1

1. Formation of digits (fingers and toes) with no programmed death of inter-digit cells (syndactyly)
2. Epi cells during palate fusion
3. Neurons in developing brain
4. Lining of gut
5. Mammary tissue after lactation (hormone deprivation)

Question 2

In neurons, what can lead to their death in terms of interaction with target cells?

Answer 2

Lack of trophic factors that leads to cells activating suicide program (apoptosis)

Question 3

What is a difference between an apoptotic cell and necrotic cell cytology?

Answer 3

Apoptotic cell: shrinks, membrane blebs, apoptotic bodies released and macrophages phagocytose, NO INFLAMM; necrotic: swell and bursts and IC contents released leading to inflamm

Question 4

If a trophic factor is present, what can be inhibited? If there is no trophic factor what can then happen? What is the pathway set off with no trophic factor?

Answer 4

Phosphorylation of Bad;
Bax-containing ion channels open with Bax not inhibited and cyt C released from mito;
procaspases proteolytically cleaved to caspases (digestion of lamins and structural proteins)

Question 5

What is terminal differentiation and what are examples of this?

Answer 5

Cells stop dividing (new set of genes for specialized function of each cell);
neurons, cardiac muscle cells, mature cells of skin epi/gut epi

Question 6

What one thing can lead to senescence? What exactly is this thing categorized as? What is the mechanism? Do most somatic cells have telomerase?

Answer 6

Absence of enzyme telomerase; ribozyme (part protein, part RNA); add 6-base repeat of non-coding DNA to parental DNA strand to allow complete synthesis of lagging strand;
Not in adult tissues

Question 7

What is p53 going to be important for?

Answer 7

Blocking entry into S phase following DNA damage or chromosomes losing their telomeres

Question 8

What are external factors for growth?

Answer 8

PDGF (released from activated platelets); EPO acts more systemically; cell-ECM matrix (anchorage-dependent cell growth with basal lamina allowing for cell proliferation in epidermis) and cell-cell interactions (contact inhibition)

Question 9

What does replication in the skin epi involve? What is the process of replication?

Answer 9

Undifferentiated stem cells;

1. SC’s attached to basal lamina that divide (anchorage dependence)
2. Decrease in integrins (decrease focal adhesions and hemi-desmosomes)
3. Detached cell will stop PROLIFERATING and differentiate!!
4. More cads/keratin to have more desmosomes between adjacent cells
5. Provide strength/buffer of skin
6. Cells die and function as barrier/strength
7. Slough off cells and replace (2-4 week cycle)

Question 10

What does the dysregulation of e.g. skin cells replicating lead to?

Answer 10

Tumor formation and progression

Question 11

What does cell adhesion stimulate? What is growth control a balance of? What are examples of this balance?

Answer 11

Convergent pathways;
stimulatory and inhibitory signals;
kinases and phosphatases, GEFs and GAPs

Question 12

What do cancer cells lack? What are the mutations that could result in most cancers?

Answer 12

Growth factor dependence; anchorage dependence; cell-cell contact inhibition; NO SENESCENCE;
Oncogenes and tumor suppressor genes

Question 13

How are oncogenes defined? How many alleles of a proto-oncogene needs to be mutated to affect cell growth? How do proto-oncogenes typically convert to oncogenes?

Answer 13

Mutated/overexpressed versions of genes normally found in cellular genomes;
ONE ALLELE!!
Result of somatic mutations (not inherited);

Question 14

What are a couple examples of oncogenic conversion? How else can you get oncogenic conversion?

Answer 14

Src non-receptor tyrosine kinase (hyperactive protein made in normal amounts because of constitutively active kinase because of mutation in neg reg of kinase);
Abl tyrosine kinase: fusion of genes giving Bcr/Abl fusion protein with constitutive kinase activity (CML);
Normal protein overproduced or strong enhancer leads to overproduction of normal protein

Question 15

What do Rb, p53, and DCC normally function to do? What activity do they have relative to proto-oncogenes? How many alleles must be defective? How can you get the mutation/deletion?

Answer 15

Inhibit cell growth and oppose activity of proto-oncogenes;
2;
First mutation/deletion can be inherited

Question 16

What does active Rb normally do? What inactivates Rb? What happens with no Rb?

Answer 16

Block transcription;
phosphorylation of Rb by active cdk/cyclin complex;
Unregulated transcription

Question 17

What can p53 do? What if it’s missing?

Answer 17

induce synthesis of G1/S cdk inhibitor p21, block Rb phosphorylation, induce apoptosis and senescence;
damaged DNA replicated;
increases prob that new mutations will be seen in progeny

Question 18

How can DNA viruses interfere with Rb and p53 function? Examples?

Answer 18

Can encode proteins from their genome to bind and sequester Rb and p53;
Papilloma virus (E6 and E7 bind to Rb and p53, respectively);
SV 40 virus: makes large T antigen to bind both

Question 19

Stages in cancer progression: list

Answer 19

1. Loss of cell division control leading to tumor (neoplasm, benign)
2. Invade and metastasize (malignant tumor and cancer)

Question 20

For the example of colo-rectal carcinoma, how many mutations are required?

Answer 20

Total of 7 (three tumor suppressor genes that require two mutations–APC, DCC, p53– and one mutation in K-Ras, a proto-oncogene)