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2012-03-30: Success for Conway scientists at 2012 IACR meeting

Three Conway scientists have been recognised for their research at the 2012 Irish Association of Cancer Research meeting, held in Belfast on March 1st & 2nd 2012.

Dr Radoslaw Zagozdzon (Prof. William Gallagher) and PhD students, Susie Boyce (Prof. William Watson) and Karolina Weiner-Gorzel (Dr Fiona Furlong) received prizes for the best poster in respective categories.

The Irish Association for Cancer Research is an All-Ireland non-profit organisation for cancer researchers that promote the exchange of ideas among researchers from different disciplines with the common goal of ultimately reducing the burden of cancer in society.

PhD student, Karolina Weiner-Gorzel presented findings from a collaborative research project jointly led by Conway fellow, Dr Amanda McCann and Dr Fiona Furlong that involves colleagues in UCD School of Public Health, Physiotherapy & Population Science as well as Trinity College Dublin, the Royal College of Surgeons in Ireland (RCSI) & Beaumont Hospital.

Ovarian cancer patients presenting with advanced stage (III/IV) cancer are treated with carboplatinum in combination with paclitaxel. Despite a significant initial response rate, fewer than 20% of patients become long-term survivors.

Karolina Weiner-Gorzel explains, “We have previously shown that low MAD2 expression levels are associated with cellular resistance to paclitaxel and that MAD2 expression levels are post-transcriptionally down-regulated by the microRNA miR-433(Furlong F., 2011).

Now we report that the microRNA miR-433 also targets the histone deacetylase 6 (HDAC6) protein in ovarian cancer cell lines. In the literature, it is known that HDAC6 promotes cell migration, invadopodia formation and angiogenesis, processes integral to tumour development and disease progression.

Intriguingly, our in vitro experiments have shown that high HDAC6 protein levels are co-expressed with MAD2 in paclitaxel resistant epithelial ovarian cancer (EOC) cells. We have also demonstrated that high HDAC6 expression levels in resistant cell lines may prevent paclitaxel-induced stabilisation of microtubules.”

The team are currently investigating the potential interaction between MAD2 and HDAC6 and their combined role predicting paclitaxel resistance in patients presenting with high grade serous epithelial ovarian cancer (EOC).

Karolina Weiner-Gorzel is supported through a Health Research Board research grant to Dr Fiona Furlong.

According to Dr Radoslaw Zagozdzon, transgenic cancer models are invaluable research tools because they recapitulate the entire process from the initial genetic events in normal cells to metastatic disease. Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points.

Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques.

‘In our project, we have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development”, explains Dr Zagozdzon. “This model, coupled with the most recent advances in the in vivo bioluminescent imaging systems, provides for a powerful, yet very feasible, tool in studies utilising genetically modified animals.

Generation of this murine strain is vital for making many of the existing mammary tumour transgenic models applicable for in vivo imaging techniques. It can also serve as a technology platform and a background strain for further development of new models.”

This material is based upon works supported by the Science Foundation Ireland under Grants No. 08/SRC/B1410 (“Molecular Therapeutics for Cancer Ireland” Strategic Research Cluster) and 07/SRC/B1163 and also by a Marie Curie International Reintegration Grant within the 7th European Community Framework Programme, and also under IRCSET Embark Initiative Postgraduate Scholarship Scheme.