A number of naturally occurring isoforms of the tumour suppressor protein p53 have been discovered, which appear to have differing roles in tumour prevention or promotion. We are investigating the tumour-promoting activities of the Δ133p53 isoform using our mouse model of Δ133p53 (Δ122p53). Here, we report that tumours from Δ122p53 homozygous mice show evidence of invasion and metastasis and that Δ122p53 promotes migration though a 3-dimensional collagen matrix. We also show that Δ122p53 and Δ133p53 promote cell migration in scratch wound and Transwell assays, similar to the 'gain-of-function' phenotypes seen with mutant p53. Using the well-defined B16 mouse melanoma metastatic model, we show that Δ122p53 leads to faster generation of lung metastases. The increased migratory phenotypes are dependent on secreted factors, including the cytokine interleukin-6 and the chemokine CCL2. We propose that Δ122p53 (and Δ133p53) acts in a similar manner to 'gain-of-function' mutant p53 proteins to promote migration, invasion and metastasis, which may contribute to poor survival in patients with Δ133p53-expressing tumours.

Neurotrophin-3 (NT-3) is essential for survival of proprioceptive and mechanoreceptor neurons, but its role in motoneuron development in vivo has seemed slight. Recent evidence however has suggested that NT-3 may be involved in motoneuron maturation. Here, we quantitatively assess the number and state of development of motoneurons within the lumbar lateral motor column (LLMC) of newborn NT-3 (-/-), (+/-) and (+/+) mutant mice. We find that the number of alpha motoneurons in the LLMC is the same in all genotypes, but soma size is significantly reduced in (-/-) mutants. This suggests that NT-3 is not required for normal production and survival of alpha motoneurons, but is essential for their full maturation and/or maintenance. We also confirm a previous report that gamma motoneurons are absent in NT-3 (-/-) mice.