Cell growth, divsion and death

Question 1

How do you calculate tissue growth?

Answer 1

cell # * average cell size

Question 2

What are the two overall factors that impact cell growth (intrinsic vs. extrinsic)

Answer 2

1) genes, developmentally programmed

2) nutrient availability

Question 3

What three things determine the cell size and the number of cells?

Answer 3

1) cell death
2) cell growth
3) cell division

Question 4

What determines cell number?

Answer 4

+ cell division

- cell death

Question 5

What determines cell size?

Answer 5

cell growth (means increase mass of individual cells)
+ synthesis of molecules/ proteins
- degradation of molecules / proteins

Question 6

Growth is (a) of division

Answer 6

UPSTREAM

Question 7

Describe genetic control of cell size based on nutrient availability

Answer 7

LOW NUTRIENTS… there are only a few ribosome per mRNA, therefore ribosome likely won’t jump across from stop codon to cyclin coding sequence…. thus no cyclin/CDK being active = cell cycle arrest

HIGH nutrients… there are a lot of ribosomes per mRNA, therefore more likely ribosome will jump across stop codon and start translation at cyclin coding sequence… this lots of active cyclin/CDK,…. which promotes G1/S transition

Question 8

Independent molecular mechanisms of cell division and growth

Answer 8

cell growth occurs INDEPENDENTLY of cell division (can occur separately)

Question 9

T or F: Growth is a consequence of division

Answer 9

FALSE

altering proliferation of cells within a tissue does not change the rate at which a tissue grows (ie. acquires mass/ cytoplasm)

Question 10

If you reduce the nutrition for a cell, the cell cycle becomes (a)

Answer 10

SLOWER… the cell waits at the G1/S transition for the cell to get big enough to divide

Question 11

Metcalf’s experiments

Answer 11

transplanted multiple spleens into newborn mice…. grew to FRACTIONAL size = systemic control (nearby organs secrete factors to inhibit growth)

transplanted multiple thymuses into mice… grew to NORMAL size = local control

Question 12

Myostatin is a systemically acting protein that

Answer 12

controls the muscle mass (ONLY IN SKELETAL MUSCLE CELLS)

Question 13

Does IGF-1 and Tsc/Tor increase or decrease cell growth?

Answer 13

IGF-1= increase in any cell that expresses IGF-1 receptor (meaning bigger cytoplasm)
Tsc/Tor = increase or decrease

Question 14

What two intrinsic pathways control cell growth?

Answer 14

IGF-1 (developmentally programmed) and Tsc/Tor (nutrient availability, calibrate growth to environment)

Question 15

Describe how IGF-1 is secreted

Answer 15

hypothalamus releases GHRH–> anterior pituitary –> released GRH or HGH —> liver–> released IGF-1–> muscle, bone, fat cells, etc.

Question 16

Describe in cell bio detail how IGF-1 increases translation & cell growth (bigger cytoplasm)

Answer 16

IGF-1 binds extracellular receptor –> activates IRS-1 –> activates PI3K (lipid kinase)–> phosphorylates PIP2 turning it to PIP3 –> PIP3 goes to internal leaflet of membrane–> activates PDK1 and AKT—> Both activate S6K (= assembling more ribosomes)

AKT inhibits eIF-4eBP, which is inhibiting eIF-4e….. eIF-4e typically is a TF for initiating translation, so inhibiting the inhibitor = more translation

Question 17

What is a brake on the IGF-1 pathway?

Answer 17

PTEN (lipid phosphatase) that converts PIP3 back to PIP2

Question 18

Describe in cell bio detail the Tsc/ Tor pathway

Answer 18

Tsc1/Tsc2—> INHIBIT Rheb (thus decreasing cell growth)

Rheb (GTPase) –> activates Tor (kinase)—> activate S6K (= assembling more ribosomes)

Nutrients from membrane nutrient importer also activate Tor (kinase)

Tor inhibits eIF-4eBP, which is inhibiting eIF-4e….. eIF-4e typically is a TF for initiating translation, so inhibiting the inhibitor = more translation

OVERALL, Tsc decreases cell growth, and Tor increases cell growth

Question 19

What drug can inhibit Tor?

Answer 19

rapamycin

Question 20

Necrosis

Answer 20

damage induced cell death (response to injury)

cell swells, release of contents, inflammation

PASSIVE PROCESS

Question 21

Apoptosis

Answer 21

programmed cell death

cell shrinks, engulfment of apoptotic body –> phagocytosis, NO inflammation, highly regulated (signal transduction)

ACTIVE PROCESS

Question 22

What enzymes drive apoptosis? and when are they active?

Answer 22

caspases!

constitutively expressed but only active once pro domain is cleaved (so only active in dying cells)… fragment genome, cleave and destroy cellular proteins, cleave and activate other proteins

Question 23

Describe in cell bio detail how caspases get active

Answer 23

Typically, Bcl2 inhibits pores in mitochondrial membrane and keeps cyt c in there

When there are intrinsic death factors (many signals)–> BH3 is activate –> inhibits BCL2—> creates pores in mitochondrial membrane—> release of cyt c and it binds with apaf-1 in the cytoplasm–> create an apoptosome (wagon wheel of death) –> activates caspase by cleavage of pro-caspase

Question 24

What are the extrinsic signals that can regulate caspases and cause mass cell death?

Answer 24

pro death ligands (ie. FASL, TRAIL, TNF-alpha)

Question 25

What issues with cells can generally cause cancer (3)?

Answer 25

1) too much cell division
2) inability to kill tumor cells
3) TOO much growth

Question 26

Oncogenes

Answer 26

when normal cellular genes become hyperactivated by 1 mutational event (genetically dominant) (normal genes= PROTO-oncogenes)

gain of function, disease promoting

Question 27

3 examples of oncogenes

Answer 27

1) point mutation: Ras
2) gene amplification: Her2/Neu
3) translocation to strong promoter: BCL2

Question 28

How does Ras work as an oncogene?

Answer 28

Ras-GTP (active) —> Ras- GDP (inactive)

point mutation leads to Ras-GTP locked in ACTIVE state = increased growth and less apoptosis

Question 29

Tumor suppressor gene

Answer 29

genes when INACTIVATED promote excess cell number or excess growth

requires 2 mutational events to inactive…. LOSS OF FUNCTION

genetically recessive

Question 30

Knudson’s 2 hit hypothesis

Answer 30

need two mutations for tumor suppressor gene to be inactivated

ie. Retinoblastoma familial vs. sporadic cases

familial (have 1 mutation already so predisposed for a 2nd… looks dominant on pedigree)

sporadic (have to have two new mutations, very rare paired events)

Question 31

What is an example of a cell cycle regulator and tumor suppressor?

Answer 31

Rb

Rb phosphorylated by CDK/cylin = inactive, which means E2F can now promote G1/S transition

Question 32

T or F: Cancer is a one step process

Answer 32

False

cancer is a multi step process

requires accumulation of alterations in oncogenes and tumor suppressor genes

Question 33

Peyton Rous experiment relating to cancer main finding

Answer 33

if you inject filtrate from a cancer chicken and inject into healthy chicken, healthy chicken gets cancer

(virus drove cell to divide by hijacking cell machinary)

discovery of oncogene technically