A mutation in the semaphorin signalling pathway and its
consequences in prostate cancer.
Doctoral thesis, UCL (University College London).
Prostate cancer kills over 10,000 men every year in the UK, mainly as a consequence of the spread of the disease to other sites in the body. It is important to understand what controls the spread of prostate cancer cells, as this may lead to treatments that either slow down or prevent metastasis, and perhaps result in the cure of some of the advanced prostate cancers. Semaphorins act as chemotactic cues for axon guidance and cell movement, via their transmembrane receptors, plexins. It has been found that semaphorins and their receptors are overexpressed in some human prostate cancer cell lines. These cell lines have been screened for mutations in genes in the semaphorin signalling pathway. 13 somatic missense mutations in the cytoplasmic domain of the Plexin B1 gene have been identified in clinical samples of primary and metastatic prostate cancers. One of the mutations C5662T was predicted to result in a substitution of a Proline to a Serine. The aim of this research is to determine if the mutation C5662T in the Plexin B1 gene alters cell behaviour and contributes to prostate cancer progression. This thesis describes the method of constructing an expression vector containing the mutation and transfecting the mutation into COS7 cells to produce stable and transient clones. The effect of the mutation on cell collapse was examined. It was possible to show that Plexin B1 is involved in cell collapse and that Rnd1 is required for this process and this effect is independent of its ligand Semaphorin 4D (Sema4D). Although no functional difference between the wild type Plexin B1 and the mutant (C5662T) was observed, the rate of cell collapse may be important and more work will be needed to define whether this is a mutation that alters prostate cancer cell behaviour.
|Title:||A mutation in the semaphorin signalling pathway and its consequences in prostate cancer|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Research Department of Urology|
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