Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Meeting report11th Lorne Cancer Conference, Lorne, Victoria, Australia, 11–14th February 1999
Section snippets
Evolving technologies
The meeting opened as a shared session with the Lorne Protein Structure and Function Meeting, focusing on modern approaches to cancer research. Julio Celis (Denmark) described how proteomics could be used to rapidly survey the identity of proteins and to quantify these changes. The current resolution of the proteomic two-dimensional (2D) PAGE is approximately 1000 molecules per cell. Proteomic 2D databases are likely to complement DNA-based databases, playing an important role in the functional
Tumor suppressors
Louise Strong (USA) summarized the cancer risks faced by Li-Fraumeni kindreds with or without identifiable p53 mutations. She highlighted the heterogeneity in risk based on factors such as smoking status, generation, age and gender (females have an apparent increased risk that is not entirely attributable to gender-specific cancers such as breast cancer). The MD Anderson group have found no difference in cancer risk or phenotype based on the site of mutation in kindreds with identifiable p53
Apoptosis
Jerry Adams (Australia) reported use of Vav regulatory sequences to provide pan-hemopoietic expression of the prototypic cell survival protein Bcl-2. The mice displayed a marked elevation in B and T lymphocyte numbers, while more modest increases were seen in other lineages, such as myeloid cells. Surprisingly, platelet numbers in peripheral blood were reduced by half, suggesting a role for Bcl-2 in megakaryocytic development or differentiation. Pan-hemopoietic Bcl-2 activation by Vav was shown
Telomeres
Fuyuki Ishikawa (Japan) established that the ATM family of genes is essential for telomere maintenance in fission yeast. He has made the novel observation of circular chromosome formation in a fission yeast mutant lacking telomeres due to defects in the ATM-homologues rad3 and a novel homologue, tel1+. Although these mutants grew poorly, occasional revertants arose with normal colony appearance. Surprisingly, mitotic function of these revertants was normal, despite the maintenance of circular
Cell cycle
Ed Harlow (USA) presented the plenary lecture which encompassed the history of the Rb family of pocket proteins with emphasis on understanding the functional role of the Rb signaling pathway and also described more recent work on the identification of new cyclin/cdk substrates. He highlighted the differences between the Rb, p130 and p107 pocket proteins in cellular differentiation, division, response to DNA damage and apoptosis. Rb−/− fibroblasts, in contrast to p130−/− or p107−/− counterparts,
Cytokines and hemopoiesis
The use of dendritic cells for immunotherapy of cancer is limited, in part, by their low representation in peripheral blood. Administration of cytokines such as GM-CSF results in an expansion of dendritic cells, but this is restricted to cells derived from myeloid progenitors. Eugene Maraskovsky (USA) described how administration of human Flt3 ligand to mice led to a large expansion of lymphoid as well as myeloid precursor populations of dendritic cells. He detailed a more recent study, in
Development
The large Eph family of receptor tyrosine kinases interact with cell membrane-bound ligands known as ephrins. Their expression during embryogenesis is thought to play a role in cell shape and motility. Caroline Brennan from the laboratory of the late Nigel Holder (UK) described a role for Eph and ephrin signaling in the patterning of presomitic mesoderm and formation of somites. Interruption of Eph signaling, achieved by injection of RNA encoding dominant-negative forms of Eph receptors and
Tumor biology
Chris Parish (Australia) purified the heparanase enzyme, previously shown to be important in tumor invasion and metastasis in animal models and in vitro, and subsequently cloned the gene. The enzyme was restricted to placenta and lymphoid organs and was upregulated in metastatic tumor cells. In parallel studies, a sulfated oligosaccharide-based inhibitor of heparanase activity (PI-88) was isolated. It has recently been shown to be an effective inhibitor of angiogenesis and tumor metastasis in
