1 November 2006
Novel breast cancer endocrine resistance genes identified
Two novel genes linked to breast cancer endocrine resistance were revealed today at Breast Cancer Campaign's first national conference in London, UK.
Speaking to Medwire News, presenting author Rajpal Burmi (Cardiff University, UK) said that the gene – GDNF receptor-?3 (GFR?3) – has never before been looked at in breast cancer, and that knockdown experiments support the idea that this and Pituitary Tumor Transforming Gene-1 (PTTG1) play a role in resistance.
The researchers believe the genes could prove useful biomarkers and therapeutic targets.
However, Burmi said he is "particularly excited" about the discovery of GFR?3 as it is a neuronal gene. There is a drive to extend work on this family of genes and the RET coreceptor, he said, noting that the coreceptor has already been evaluated in lung cancer.
The results come from a microarray study of 12,000 genes from models with acquired resistance to tamoxifen or faslodex, which Burmi pointed out is "a step up" from simple in vitro work.
Alongside breast cancer genes already implicated in endrocrine resistance – including beta-catenin, PIA3, vitronectin, and CD44 – they detected increased levels of the securin/cell cycle regulator PTTG1 and GFR?3, which reportedly promotes cell survival via the RET co-receptor.
Altered levels of PTTG1 and GFR?3 were also seen in cells resistant to estrogen deprivation, and the genes were implicated in resistance to anti-epidermal growth factor receptor agents currently in development.
Knockdown of the expression of both genes using small interfering RNA inhibited proliferation and promoted cell death, the team reported.
They concluded: "Cumulatively, these data indicate PTTG1 and GFRalpha2 may provide useful biomarkers, and perhaps clinically relevant therapeutic targets fro multiple resistant states."
Breast cancer research: the past and the future; London, UK: 1 November 2006
http://www.breastcancercampaign.org/...ic_conference/
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