Al and polyclonal antibodies developed in-house. This is an important development
Al and polyclonal antibodies developed in-house. This is an important development because most previous work on ER has been at the mRNA level. Analysis of breast tumours revealed nuclear ER immunoreactivity, but there were no associations with known clinical prognostic markers, highlighting the fact that ER may have a distinct biological role and is not just a surrogate for ER. Cell line work showed a differential response to 17-oestradiol depending on which ER subtype was expressed, further emphasizing the distinct biological roles of the and receptors. Exon 5deleted ER variants were also detected in cell lines. This was expanded further by Eli Gilad (Lawrence Berkeley National Laboratory, Berkeley, CA, USA) who showed that expression of this variant acts as a dominant-negative mutant to ER. In an eloquent talk by Heather Cunliffe (National Human Genome Research Institute, Bethesda, MD, USA, and recipient of an AACR rtho Biotech, Inc, Young Investigator Scholar Award), the role of the steroid receptor coactivator AIB1 was discussed. AIB1 is a receptor coactivator of the p160 family, which is amplified and overexpressed in 10 of breast cancers. Using a range of ER+ cell lines, recruitment of AIB1 into ER estrogen response element complexes was demonstrated, emphasizing the functional significance of this coactivator in breast tumours with AIB1 amplification.breast cancer, and harbours several cancer-associated genes, including the tumour suppressor gene p53, BRCA1 and c-erbB2. An expression survey of gene transcripts revealed amplifications of RAD51C, S6K, PAT1 and TBX2, as well as a novel highly amplified expressed sequence tag on the 17q23 amplicon. Together with better-characterized genes, these candidates may contribute to breast cancer development. There were also examples of coupling this technique with another emerging technology, laser capture microdissection, which illustrates its sensitivity. In the late-breaking abstract section, John Bartlett (University of Glasgow, Glasgow, UK) described the use of genomic microarrays to detect copy changes in microdissected breast tumours. In Vorapaxar site contrast to standard comparative genome hybridization (CGH) protocols, this `CGH-on-a-chip’ has the added benefit of defining specific regions that are reported PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27196668 to be amplified in breast tumours, and has widespread application in determining the molecular events that underlie disease progression and patient outcome. Clearly, this is a burgeoning area; identification of novel genes associated with the genesis of breast cancer will surely lead to a better understanding of the processes involved, which may have potential for developing novel treatment strategies in the future.Microenvironmental contributions to tumour progressionA growing number of investigators are recognizing that, in addition to the chromosomal abnormalities and genetic lesions that destabilize homeostatic cellular function, tumour progression is largely influenced by the tissue microenvironment, that is, the matrix and cellular components of a given tissue type. Mina Bissell (Lawrence Berkeley National Laboratory, Berkeley, CA, USA) described the mammary epithelial cell models used in her laboratory to understand the mechanisms by which cells normally perceive the surrounding microenvironment and how, as cells become tumourigenic, they lose their ability to sense and respond appropriately to cues in the surrounding milieu. Recent work showed that effective communication between a.