DNA repair .. continued Flashcards
The use of cultured cells to study secondary events in tumour formation. Explain Crisis ?
Most cells die after culture within
a few weeks (crisis)
What happens to the cells which survive crisis? and how ?
They are an established cell line and grow indefinitely, with the following characteristics:
- Anchorage dependence
- Growth factor dependence
- Show density-dependent inhibition
- Morphology
Explain Anchorage dependence ?
Cells need a surface to attach to
Explain Growth factor dependence ?
Require essential growth factors and hormones to survive
Explain Show density-dependent inhibition ?
Cells only grow to a limited density due to cell-cell contacts
Explain the morphology?
Cells are flat and extended on the growing surface, typical with an elongated network of stress fibres
What do the cells which become transformed show many characteristics of ?
Tumour cells, with the following:
- Anchorage independence
- Less growth factor dependence
- Lack density-dependent inhibition
- Increased metabolic rates
Now explain the growth characteristics of tumour cells in culture ?
- Anchorage independence; cells do not always need a solid surface to attach to and are more resistant to apoptosis
- Less growth factor dependence; some cells even make their own growth factors for autocrine stimulation and survival
- Lack density-dependent inhibition; show decreased levels of contact inhibition and grow on top of each other
- Increased metabolic rates; increased expression of glucose transporters or ones with increased activity; secrete lactic acid (WARBURG effect) which changes the colour of the growth medium; increased rates of protein synthesis
What does altered morphology show in cells?
Decreased expression of surface fibronectin and exhibit increased motility; cells round up and lose attachment with the surface
What else does the altered morphology in a cell show ?
Decreased cytoskeletal arrangement due to disarray, decreased expression or aberrant expression of essential structural proteins (e.g. tropomysin, actin, vinculin)
Malignant tumours cells are invasive and can spread. This process requires a number of events, including:
- A number of changes in gene expression
2. The ability to move brought about decreased fibronectin/E-cadherin expression to reduce cell:cell contacts
What does decreased E-cadherin and increased N-cadherin expression reduce ? and alter ?
It reduces cell to cell contact. This alters cell signalling