Angiogenesis

Role of Raf in vascular protection from distinct apoptotic stimuli. Alavi, A. et al. Science 301, 94–96 (2003)

Alavi et al. investigated angiogenic pathways in endothelial cells (ECs) activated by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) showing that VEGF prevents receptor-mediated apoptosis, whereas bFGF protects cells from stress-mediated death. RAF1 — associated with EC survival — is activated by p21-activated protein kinase (PAK) or SRC kinase. Mutation analysis of RAF1 showed PAK is crucial for bFGF-mediated protection from apoptosis, whereas SRC is essential for the protection mediated by VEGF. These findings indicate that RAF1 is important for EC survival during angiogenesis.

Immunotherapy

Immunotherapy of established tumors using bone marrow transplantation with antigen gene-modified hematopoietic stem cells. Cui, Y. et al. Nature Med. 9, 952–958 (2003)

If tumour antigens can be efficiently transferred to antigen-presenting dendritic cells (DCs) in vivo, cancer vaccines will be more effective for immunizing against tumours. Cui et al. used haematopoietic stem cells (HSCs) engineered to express tumour-antigen-encoding genes and transplanted them into irradiated mice generate efficient transgene expression in the mouse DCs. Administration of DC-activating agents and mature T cells with the transplanted HSCs, led to marked expansion of antigen-specific T cells and successful treatment of established tumours.

Mouse Models

Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry. Sage, O. J. et al. Nature 424, 223–228 (2003)

Germline alteration of genes in mouse models is often used to study human cancer. However, Sage et al. show that a conditional knockout of the retinoblastoma (Rb) gene in mice does not have the same effect as germline loss of Rb function. The authors show that acute loss of Rb is sufficient for cell-cycle entry. Use of conditional knockouts might enable more accurate study of the effects of spontaneous mutations in human cancers.

Tumour suppressors

OPCML at 11q25 is epigenetically inactivated and has a tumor-suppressor function in epithelial ovarian cancer. Sellar, G. C. et al. Nature Genet. 34, 337–343 (2003)

Loss of heterozygosity at 11q25 has been shown to be associated with sporadic epithelial ovarian cancer. Sellar et al. have now identified a candidate tumour-suppressor gene at this locus — OPCML — that is a member of the immunoglobulin-domain-containing GPI-anchored cell-adhesion molecules.