Session 2 - Growth Factors and Receptors Flashcards
Give two main forms of extra-cellular signalling molecules
- Polypeptides (growth factors)
a. act through receptors on the cell membrane
e. g. hormones and cytokines - Low molecular weight molecules
a. these traverse the cell membrane and bind to intracellular receptors
Give three methods of extracellular signalling
Endocrine
Paracrine
Autocrine
What is endocrine?
hormones transported by the blood stream
Paracrine?
Molecule produced locally by one cell and has effect on another cell
Autocrine
Molecule produced locally and has same effect on same cell
What are growth factors?
Growth factors are ligands which bind to growth factors receptors on cell membranes, inducing intracellular signal transducers and subsequently transcription factors in order to have an effect on the growth and development of a cell.
Give three roles of growth factors
- Regulation of growth (can inhibit as well as stimulate)
- Inducing maturation and maintain differentiation in normal tissues
- Have an important role in healing and repair
Give five types of growth factor
Platelet Derived Growth Factor Fibroblast Growth Factors Epidermal Growth Factor Transforming Growth Factor A Transforming Growth Factor B
What produces platelet derived growth factor?
Platelets and other, non-platelets
What does PDGF do?
. Stimulates proliferation of stromal cells and endothelial cells by paracrine mechanisms and is therefore important in angiogenesis.
What do fibroblast growth factors do?
Stimulate proliferation of fibroblast, endothelial cells and smooth muscle cells. Also angiogenic.
Give two examples of cancers in which Epidermal Growth Factor Receptor is targeted
Breast and lung cancer
What does transforming growth factor A do normally?
Induces epithelial development.
What does TGF A do in breast cancer?
Mediates mitogenic effects of oestrogen and is responsible for autocrine growth stimulation
What five jobs does Transforming Growth Factor B do?
acts as a growth inhibitor in epithelial cells, but a growth stimulator in fibroblasts. Stimulates production of extracellular matrix by increasing synthesis and decreasing degradation. Also mediates immune system by blocking activation of lymphocytes/macrophages and can stimulate angiogenesis.
What role does TGF B have in cancer?
By promoting angiogenesis and blocking and immune response to the cancer.
Give two types of growth factor receptor?
- Serine/Threonine Kinases
- Tyrosine Kinase Receptors
Give an example of Serien/Threonine Kinases?
A receptor found in many cancers, examples include both types (1 and 2) of the receptor for Transforming Growth Factor B.
Give three examples of tyrosine kinase receptors
- Type 1 – Epidermal Growth Factor Receptor
- Insulin Growth Factor Receptor
- PDGF receptor
What cancers are Epidermal Growth Factor Receptors involved in?
Squamous Carcinomas and activating mutations in lung cancer
Where are HER-2 receptors found, and in what cancer aeitologies does it cause problems?
gene amplification and over-expression is found in adenocarcinomas and 20% of breast cancer
How do you treat HER-2 positive breast cancer?
Herceptin
Give two examples of steroid hormones
Androgens
Oestrogens
What cancers are androgens involved in?
gene amplification and over-expression is found in adenocarcinomas and 20% of breast cancer
Give two cancers oestrogen is involved in?
Breast and endometrial cancer
What does retinoic acid do?
Induces differentiation in cancer cells of Acute Myeloid Leukaemia, therefore slowing disease progression
What are the three main domains of steroid receptors?
- Hormone binding
- DNA binding
- Transactivating (induce transcription)
Give the sequence of events of steroids interacting with receptors?
Steroids interact with receptor -> Specific binding to hormone response element in DNA -> Transcription factors and RNA polymerase recuited to iniate transcription of target genes _> Protein synthesised -> Functional response
How do cancer cells interact with growth factors differently to normal cells?
They have a lower requirement for growth stimulatory molecules and a diminished sensitivity to inhibitory signals.
Give a process cancer cells require growth factors for?
Angiogenesis
Give two ways in which growth factors may be produced by cancer cells?
cancer cells themselves or by inducement of benign cells around the tumour
How is platelet derived growth factor involved in chronic myeloid leukaemia?
• Translocation between chromosomes 5 and 12 leads to formation of fusion gene, with resulting misguided activation of PDGFRB. This is an early event in development of chronic myeloid leukaemia, highlighting the oncogenic potential of PDGF.
How has the treatment of lung cancer changed in the last twenty years?
Past
Small cell or non-small cell
Now
Small cell, non-small cell (Squamous cell? If not, adenocarcinoma? If so, EGFR positive or negative?
What is a fusion gene?
Forms a receptor which is always on
What is the difference in cell staining in polypeptide and steroid receptors?
Polypeptide - Cell surface
Steroid - within cell
