Poster Presentation 25th Lorne Cancer Conference 2013

A FUNCTIONAL IN VIVO shRNA SCREEN FOR BREAST CANCER METASTASIS SUPRESSOR GENES (#382)

Rebeka Tomasin 1 2 , Richard P Redvers 1 , Kaylene J Simpson 1 , Robin L Anderson 1
  1. Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia
  2. State University of Campinas, Campinas, SP, Brazil

When diagnosed early, breast cancer can be treated with a high degree of success. However, once the disease reaches metastatic stage, when the cancer spreads to distant organs such as lungs and bone, the treatments are extremely limited and the prognosis is very poor. By identifying genes that control metastasis, it will be possible to predict those patients whose disease is likely to spread and also create an opportunity to develop more efficient therapies. Using a poorly metastatic mammary tumour cell line (66cl4ch14), we initiated a genome-wide in vivo shRNA screen to identify genes whose reduction in expression levels leads to metastasis to secondary sites. Four candidate genes, whose loss of function increased metastasis to bone in vivo, were identified in the preliminary screen: Hsd17b13, Muc15, Pdlim1 and Ndufa4. Interestingly, three of four are significantly downregulated in human aggressive breast carcinomas in comparison with normal breast tissue (Oncomine). These four candidate genes are now under additional analysis to be validated as metastasis suppressor genes. Additional screenings using the shRNA library are also ongoing aiming to identify additional breast cancer metastasis regulators genes.