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Flashcards in Growth Factors And Receptors Deck (37)
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1
Q

What are the three types of extracellular signals? Define each one

A

Endocrine - transported by the bloodstream to affect distant sites and tissues

Paracrine - molecules produced locally by one cell that have an effect on another

Autocrine - molecule produced locally and has an effect on the same cell

2
Q

How are growth factors produced?

A

Synthesised as large precursors

Cleaved by protease so to monomers

3
Q

How do growth factors exert their effects?

A

Bind to growth factor receptors in the cell membrane

Induce intracellular signal transducers which affect transcription factors

4
Q

What can be the overall effects of growth factors?

A

Can stimulate or inhibit growth

5
Q

Function of platelet-derived growth factor?

A

Stimulates proliferation of stromal cells and endothelial cells by paracrine mechanisms - important for angiogenesis

6
Q

Where in platelets is PDGF found?

A

In their granules

N.B. can also be produced by non-platelets

7
Q

Function of fibroblast growth factors?

A

Stimulate proliferation of fibroblasts, endothelial cells and smooth muscle cells - important for angiogenesis

8
Q

Function of transforming growth factor α?

A

Induces epithelial development

9
Q

Function of transforming growth factor β?

A

Acts as a growth inhibitor of epithelial cells
Stimulates growth of fibroblasts
Stimulates production of extracellular matrix by increasing synthesis and decreasing degradation
Blocks activation of lymphocytes and macrophages
Can stimulate angiogenesis

10
Q

How do growth factor receptors transducer the signal?

A

Binding of the ligand (growth factor) causes a conformational change in the receptor which activates the cytoplasmic tail

11
Q

Give some examples of growth factor receptors

A

Serine/threonine kinase

Tyrosine kinase receptor

12
Q

What can drive growth of a tumour?

A

Changes in the growth factor receptors

13
Q

How can cancer cells be stimulated by growth factors - like where do the growth factors come from?

A

Can be stimulated by systemic growth factors
Can produce their own growth factors
Induce surrounding benign cells to produce growth factors

14
Q

Which growth factors can be used for angiogenesis?

A

PDGF

Fibroblast growth factors

15
Q

What is HER2?

A

A gene that codes for a co-factor for EGFR and is seen in many breast cancers
Also now targeted in lung cancers

16
Q

In cancer, what does transforming growth factor α do?

A

Induces epithelial development
In breast cancer
-responsible for autocrine growth stimulation
-mediate mitogenic effects of oestradiol

17
Q

Function of transforming growth factor β in cancer?

A

Promote angiogenesis
Block them immune response
Inhibitory pathway often muted in cancer cells

18
Q

What can bind to epidermal growth factor receptors?

A

EGF

TGF-α

19
Q

What happens to EGFRs in many cancers? Which types in particular?

A

Amplified

Seen in squamous carcinomas and activating mutations in lung cancer

20
Q

What can cause genetic changes to TGFβ receptor II?

A

Microsatellite instability - the condition of genetic hyper mutability that results from impaired DNA mismatch repair

21
Q

What does the HER-2 receptor normally do?

A

Forms dimers with other type I tyrosine kinase receptors

22
Q

What can happen to HER2 to lead to cancer?

A

High expression - get gene amplification and over-expression in adenocarcinomas

23
Q

What can cause activation of PDGFR(B) receptor? Which cancers is it seen in?

A

Translocation between chromosomes 5 and 12 to form a fusion gene
An early event in development of chronic myeloid leukaemia

24
Q

What are some hydrophobic growth regulatory molecules?

A

Steroids - androgens and oestrogens
Thyroid hormone
Retinoic acid (metabolised Vit A)

25
Q

Which cancers are androgens and oestrogens promoters in?

A

Prostate cancer

Breast and endometrial cancer

26
Q

How can vitamin A slow progression of acute myeloid leukaemia?

A

Metabolised to retinoic acid

Induces differentiation in cancer cells of AML - slowing disease progression

27
Q

What are the three domains that steroid receptors share?

A

Hormone binding domain
DNA binding domain
Transactivating domain - induces transcription

28
Q

What happens when a steroid bins to the receptor?

A

Steroid binds to receptor
Receptor binds to hormone response element in DNA
Transcription factors and RNA polymerase are recruited to initiate transcription of targeted genes
Protein is synthesised and get a functional response

29
Q

What are the two types of oestrogen receptors and where are they present?

A

Classical or α form - present in breast, endometrium and myometrium

Secondary or β form - wider distribution

30
Q

What happens when receptors are bound to the hormone?

A

Receptor forms dimers which may be homo or heterodimers (αα, ββ or αβ)

31
Q

How are oestrogen receptors detected in tissue?

A

Immunohistochemistry - use routine pathology material

32
Q

Name some of the receptors in the steroid receptor family

A
Glucocorticoids
Progesterone
Androgen
Oestrogen 
Mineralocorticoids 
Thyroid
Retinoic acid 
Vitamin D
33
Q

How can mutations causing upregulation of EGFR be detected?

A

Detect mutations by qPCR or sequencing methods

34
Q

How can detecting mutations activating EGFRs be a predictive marker of cancer? Which cancer is it used for?

A

Can target therapies - gefitnib

A minority of lung cancers

35
Q

So in general, which two types of receptors can growth factors act on?

A

Transmembrane receptor with intracellular kinase domains

Directly on nuclear transcription factors

36
Q

How can growth factors and receptors drive tumour growth?

A

If there is over expression of factors
Over expression of receptors
Alterations in receptors

37
Q

What are the two main forms of extracellular signalling molecules and how do they exert their effect at the target site? Give examples for each

A

Polypeptides (growth factors) - act through receptors in the cell membrane eg hormones and cytokines

Low molecular weight molecules - traverse the cell membrane and bind to intracellular receptors eg steroid hormones