Therapeutics

Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts.Berg, T. et al. Proc. Natl Acad. Sci. USA 99, 3830–3835 (2002)

MYC–MAX heterodimers drive oncogenic transcription, so Thorsten Berg and colleagues searched for molecules that block this partnership, using a simple in vitro assay. The authors screened 7,000 compounds for a drop in energy transfer (FRET) between fluorescently labelled MYC and MAX proteins. Two compounds inhibited the transformation of chick fibroblasts, as well as blocking MYC–MAX interaction.

Genomic instability

Disruption of Brca2 increases the spontaneous mutation rate in vivo : synergism with ionizing radiation.Tutt, A. N. J. et al. EMBO Rep. 3, 255–260 (2002)

Do mammography and radiotherapy pose an additional cancer risk for women with BRCA2 mutations? A mouse model that combines a Brca2 truncation mutation (Brca2Tr) with a reporter gene that allows measurement of spontaneous mutation has been used to show that Brca2Tr/Tr mice have more spontaneous and ionizing-radiation-induced mutations than wild-type mice. Mutation rates in Brca2Tr/+ mice and wild-type mice are similar, indicating that BRCA2-mutation carriers are not at increased risk from radiation exposure.

Tumour suppressors

Induction of p57KIP2 expression by p73β.Bálint, E. et al. Proc. Natl Acad. Sci. USA 99, 3529–3534 (2002)

The transcription factor p73 acts similarly to its homologue p53 in its ability to induce cell-cycle arrest and apoptosis. But, despite their ability to activate expression of many of the same genes, their functions are distinct — only p73 is involved in normal growth and development. Éva Bálint et al. now show that the p73β isoform activates CDKN1C, which encodes the cyclin-dependent kinase inhibitor KIP2, and KvLQT1, both of which reside in an imprinted region of the genome and are involved in development.

Signalling

Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy.Dias, S.et al. Blood 99, 2179–2184 (2002)

Leukaemia cells release pro-inflammatory cytokines and pro-angiogenic factors in autocrine loops that promote leukaemic-cell growth and migration. A vascular endothelial growth factor family member, VEGFC, has similar effects: VEGFC treatment induces receptor phosphorylation, proliferation and increased survival in leukaemia cells in vitro. Moreover, VEGFC protected the cells against the apoptotic effects of three chemotherapeutic agents, so it might be involved in cancer drug resistance.