Lecture 19 - Growth Control

Question 1

Do all cells grow at the same rate?

Answer 1

No - there are some cells that divide rapidly (small intestine, epidermis), so slow/never (neurons)

Question 2

What combination of factors leads to grow control?

Answer 2

1. Cell lineage
2. External/diffusible factors (i.e. growth factors)
3. Cell-cell/cell-ECM interactions

Question 3

Is apoptosis a normal occurence during development?

Answer 3

Yes! Programmed cell death occurs to prevent syndactyly

Also is result of checkpoint error in DNA replication/cell cycle

Question 4

Describe the apoptosis in neuronal development

Answer 4

Nerve cell bodies have a 1:1 relationship with Target cells, extraneous nerve cells are apoptosed.

Trophic factors are required for the nerve cells to live - in their absence, apoptosis is induced

Question 5

Describe the appearance of apoptosic cells in general

Answer 5

Shrunken cells w/ membrane blebs and then fragment, releasing small membrane bound blebs >>> then taken up by macrophages

Intracellular contents not released (compared to necrotic cells), prevents inflammation

Question 6

Describe the pathway when trophic factors are present

Answer 6

When trophic factors are present, BAD is phosphorylated, where cytochrome C is not released and caspase cascade not induced

Question 7

Describe the process when trophic factors are NOT present

Answer 7

BAD not phosphorylated, Bax channel opens, leading to efflux of cytochrome C >>> caspase cascade

Question 8

Terminal differentiation

Answer 8

Cells stop dividing after a pre-set number of divisions and take on a differentiated phenotype (RBC, neuron)

Question 9

Senescence

Answer 9

Cells in culture stop dividing after about 50-100 divisions (due to absence of telomerase in adult cells)

When telomeres get too short > p53 activated > p21 cdk inhibitor (blocks cells in G1 > senescence

Question 10

What are the external influences that affect growth?

Answer 10

1. Growth factors - diffusible signaling molecules, can act locally or systemically (ex. erythropoietin)
2. Cell-ECM interactions - normal cells fail to divide if they’re deprived of interaction w/ insoluble matrix (anchorage-dependent cell growth)
3. Cell-cell interactions - normal cells exhibit density dependent growth inhibition (contact inhibition)

Question 11

How are different tissues (nerve/cardiac muscle/liver/skin) maintained?

Answer 11

Nerve and cardiac muscle cells are permanent cells - survive as long as the organism

Liver replications by simple duplication

Skin regenerates from undifferentiated stem cells (basal lamina)

Question 12

Describe the signaling cascades of growth

Answer 12

Growth control is a balance of stimulatory and inhibitory signals (ex. kinases and phosphatases)

Question 13

How do cancer cells differ from “normal” cells?

Answer 13

Cancer cells may have some of these characteristics:

They do not senesce

Lack growth factor dependence

Lack anchorage dependence

No cell-cell contact inhibition

Most cancers stem from mutaiton of oncogenes and tumor suppressor genes

Question 14

Oncogenes

Answer 14

Disregulated (mutated or overexpressed) versions of genes normally found in cells (these are called proto-oncogenes)

Conversion from proto-oncogene to oncogene usually result of somatic mutaiton

Question 15

Give some characteristics of proto-oncogenes

Answer 15

Proteins that normally stimulate growth

Conversion to oncogene results in elevated and/or unregulated activity

Mutation of SINGLE allele of proto-oncogene can cause abnormal growth

Question 16

Tumor suppressor genes

Answer 16

Genes normally found in cellular genomes

Normally function to oppose activity of proto-oncogenes (normally inhibit growth)

Cells lose growth control when these are mutated to inactive form

Both alleles must be mutated or deleted (loss of heterozygocity)

First mutation/deletion is often inherited (individuals are predisposed to developing cancer)

(Ex. Inactive Rb protein leads to retinablastoma, mutated p53)

Question 17

Describe actions of viral proteins on Rb and p53

Answer 17

DNA viruses carry genes that encode proteins that block Rb and p53

Leads to hyper proliferation of cells

Occurs in HPV

Question 18

What are the stages in cancer progression?

Answer 18

Loss of cell divisions/growth control > Tumor (neoplasm) > Ability to invade/metastasize > Malignant tumor > Cancer

Question 19

The development of cancer takes at least how many mutations?

Answer 19

7 - tumor suppressors (2 mutations each), proto-oncogenes (1 mutation)