Tumour Suppressors

The regulation of exosome secretion: a novel function of the p53 protein Yu, X. et al. Cancer Res. 66, 4795–4801 (2006)

p53 is a transcription factor that is activated in response to cellular stress. Yu et al. have used a proteomics approach to identify proteins that are secreted by cells in a p53-dependent manner after DNA damage. p53 activation was found to increase the secretion of a set of proteins that are encoded by genes that are not transcriptional targets of p53. These proteins are secreted through small vesicles called exosomes. Furthermore, exosome production by cells is regulated by activation of the p53 pathway, so this pathway has a newly-discovered function in the communication between cells.

MicroRNA

Pre-B cell proliferation and lymphoblastic leukaemia/high-grade lymphoma in Eμ-miR155 transgenic mice Costinean, S. et al. Proc. Natl Acad. Sci. USA 103, 7024–7029 (2006)

MicroRNAs (miRNAs) are small, non-coding RNAs that are involved in post-transcriptional regulation of gene expression. The miRNA miR155 has previously been shown to be highly expressed in human B-cell lymphomas. Now, Crostinean et al. show that transgenic mice that carry an miR155 transgene, the expression of which is targeted to B cells (Eμ-miR155), show preleukaemic pre-B-cell proliferation, and later develop a B-cell malignancy. miR155 might be a new target for the treatment of B-cell cancers.

Oncogenes

Reversible kinetic analysis of Myc targets in vivo provides novel insights into Myc-mediated tumorigenesis Lawlor, E. R. et al. Cancer Res. 66, 4591–4601 (2006)

The transcription factor MYC is frequently deregulated in human cancers. Lawlor et al. used a reversible-switch transgenic model of MYC-mediated β-cell tumorigenesis, in combination with oligonucleotide microarrays, to identify MYC-regulated genes that are responsible for maintaining MYC-dependent tumours. In addition to genes involved in cell proliferation and tumour progression, a proportion of the MYC-regulated genes were found to be β-cell specific, which indicates that MYC action is, in part, cell-type specific.

Tumour Immunology

IL-23 promotes tumour incidence and growth Langowski, J. L. et al. Nature, 10 May 2006 (doi:10.1038/nature04808)

Langowski et al. show the first molecular connection between tumour-associated inflammation and the failure of the adaptive immune response to target tumours. They show that expression of the cytokine IL-23 is increased in human tumours, and that this both promotes the inflammatory response and reduces cytotoxic T-cell infiltration. Inhibition of IL-23 increased tumour infiltration by cytotoxic T-cells, and the growth of transplanted tumours was reduced in mice that were depleted of IL-23. So, anti-IL-23 therapy might prove to be an effective treatment for solid tumours.