tissue renewal, stem cells and cancer

Question 1

cancer cells have defects in which genes

Answer 1

proliferation (proto-oncogenes) genes and anti-proliferation genes

Proliferation- activating mutations- oncogenes (cancer version)

Anti-proliferation- loss/inactivation- act as tumour suppressor genes normally, but when lost cell division gets out of control

Question 2

Proto-oncogenes and tumour supressor genes encode

Answer 2

a number of different types of protein

Question 3

Oncogenes promote

Answer 3

inappropriate cell proliferation

Question 4

In absence of signal binding to cell receptor, how can cell proliferation still occur

Answer 4

may have abnormally active mutant intracellular signalling protein, which can provoke response in the cell with absence of of growth factor/signal

Question 5

Tumour supressors

Answer 5

part of cell cycle ‘braking’ mechanism

Question 6

Example of tumour supressor

Answer 6

Rb
Phosphorylated by G1/S cyclin/cdk to become active
If Rb were to become mutant, wouldn’t be able to inactivate S phase TFs so would the TFs would be active constantly, leading to incr cell proliferation

and p53

Question 7

Example of oncogene

Answer 7

cyclins

Active inappropriately- proliferation occurs inappropriately

Question 8

tissue organisation

Answer 8

highly organised mixture of many cell types

eg cells closer to surface of skin more specialised, flatten and loose nuclei as move to skin surface

Question 9

Epidermis

Answer 9

continually renewing barrier

Question 10

Dermis

Answer 10

provides mechanical support

Question 11

layers of skin outermost to innermost

Answer 11

epidermis, loose then dense connective tissue of the dermis, fatty connective tissue of the hypodermis

Question 12

What are all skin layers infiltrated by

Answer 12

sensory nerves and BVs

need other specialised cell types to permeate tissue and bring BVs etc in

Question 13

Cells in the epidermis

Answer 13

mainly keratinocytes
also pigment cells (melanocytes)
Langerhans cell (involved in immune responses)
Great degree of organisation even in outer layer

Question 14

Cells in the dermis

Answer 14

Lots of fibroblasts
Collagen fibres and ECM which provide support
mechanical strength and flexibility
Elastic fibres in dense epidermis running in 2 directions

Question 15

3 key factors which maintain cell organisation

Answer 15

cell communication , selective cell-cell adhesion (cells in layers use cell adhesion to assemble as a layer), cell memory (cell has a memory of its developmental history- can reach the point where it performs its specialised function)

Question 16

Rate of cell renewal

Answer 16

Cells renewed a different rates according to function of the tissue

least- most
neuron, bone, epidermal, RBC, gut epithelial`

Question 17

What cells key to renewal

Answer 17

stem

can repl itself and then differentiate

Question 18

ESCs

Answer 18

can give rise to all cell types
inner cell mass in the blastocyst
Outer cells form placenta

Question 19

multipotent SCs example

Answer 19

bone marrow SCs can give rise to all blood cell types

Question 20

Unipotent SCs example

Answer 20

SCs in basal epidermis give rise to skin keratinocytes

Question 21

Oligopotent SCs example

Answer 21

Gut epithelial SCs give rise to a few terminally differentiated cell types eg goblets

Question 22

Cell renewal in the skin process

Answer 22

Transit amplifying cells divide, start to differentiate
Express different cell adhesion molecules, lose recognition of neighbours in basal layer (lower epidermis) and begin to adhere to cells above them. Pushed towards the surface of the epidermis

As they move they flatten, nuclei dismantled, end up as dead flattened cells which are shed

Question 23

epithelial lining of the small intestine

Answer 23

Stem cells in the base of crypts
As cells move out of the crypts and up into the villus they differentiate into eg goblet cells, brush border cells which absorb nutrients

Each crypt has 1-3 SCs, move up and go through trans-amplifying stage and at top of crypt begin to differentiate. Specific signals for switch form division to differentiation (WNT signalling)

Question 24

WNT signalling

Answer 24

one of the targets is LGR5- key marker and TF expressed only in the SCs

Question 25

wnt pathway inactive

Answer 25

no cell proliferation

Question 26

Blood cell differentiation

Answer 26

All come for haematopoetic SCs located in bone marrow

Question 27

treating blood disorders using Stem cell therapies

Answer 27

Treatment of leukemias takes adv of bone marrow SCs Patients own Bone marrow cells destroyed by radio/chemotherapy- Bone marrow replaced by transplanation of donor bone marrow (better than blood transfusion- short term fix) Work because blood SC pool replaced

Question 28

iPS

Answer 28

Introduce 3 TFs into any cell in the body, transformed to become ESC like

Question 29

Human iPS cells uses

Answer 29

disease modelling and toxicology (drugs) Regenerative medicine (as opposed to hES- human embryonic stem cells- have ethical problems)

Question 30

can make human iPS's from

Answer 30

skin fibroblast

Question 31

In cancer what goes wrong (skin)

Answer 31

controls over cell proliferation and survival breakdown, first through mutation in individual cells. The mutation gives one cell an adv, and a second mutation gives a further advantage Third mutation incr adv further and cell becomes invasive- mutation spread into surrounding healthy cells. This is now a benign tumour. Becomes more dangerous when these cells move away from their site- break down basal lamina that separates them from other tissues, then invade those tissues. Find blood or lymphatic vessels and cells get through endothelium into these vessels- metastasis eg in the liver

Question 32

Polyp in the gut

Answer 32

small tumour growth polyp= projects from mucous membrane Can be benign, but if start to accumulate mutations eg loss of tumour supressor,

Question 33

P53 gene lost

Answer 33

recognition usually for dna damage. Can accumulate mutations more rapidly because lost function for identifying and fixing mutations