Results: Seven up-regulated genes were confirmed modulated (RT-qPCR analysis) in the cell transformation model after VD treatment (24 h), including BMP6 and DPP4. Among them, CD14, IL1RL1 and SHE were also modulated in MCF7 cells. Despite constant levels of CD14 protein in all cells, a significant increase in sCD14 was seen. Conversely, Vorinostat ic50 detectable CA2 protein levels were present only in HME and HMELT VD treated cells. Conclusion: Novel VD regulated genes were identified in this model, some of them probably influenced by the stromal compartment. Supported by FAPESP 2007/04799-2, CAPES, NIH CA69700. Poster No. 23 Siah2 Controls Breast Cancer Progression through Tumor Epithelial

Cell Mediated Cytokine Release and Stromal Infiltration Christina Wong1, Colin House1, Mira Liu1, Izhak Haviv3, David Small molecule library Bowtell1,2, Andreas Moeller

1,2 1 Department of Research, Cancer Genomics and Biochemistry Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, 2 Department of Biochemistry and TNF-alpha inhibitor Molecular Biology, University of Melbourne, Parkville, VIC, Australia, 3 Department of Research, Baker IDI Heart and Diabetes Institute, Prahran, VIC, Australia In estrogen receptor positive breast cancer, one of the most significantly upregulated genes is the ubiquitin ligase Siah2. Knocking out Siah2 significantly delays the onset of breast cancer in the PyMTAg-derived breast cancer mouse model. Mammary epithelial cells from Siah2 knockout mice produce and secrete elevated levels of cytokines, including CXCL10 and GM-CSF. On a molecular level, this is caused

by constant nuclear NFkB localisation and a higher sensitivity to TNFalpha-mediated activation, identifying Siah2 as a novel negative regulator of this tumor progression pathway. The elevated cytokine secretion in turn results in increased immune cell infiltrate in the mammary glands, suggesting increased immune surveillance. Siah2 knockout tumor cells from mice with tumors at advanced stage have strongly reduced stroma. This is caused by the inability of the Siah2 knockout NADPH-cytochrome-c2 reductase host stromal cells to respond to attraction signals derived from the tumor epithelium. Further evidence for this is supported by data from in vitro work and in transplanted tumor models showing that Siah2 knockout tumor cells can recruit stroma to the tumour in wildtype mice, whereas wildtype tumor cells growing in Siah2 knockout mice are not associated with stromal infiltration. Poster No. 24 Evaluation of Periostin Isoforms in the Tumor Microenvironment of Lung and Kidney Cancer Laura Morra 1 , Peter Schraml1, Holger Moch1, Alex Soltermann1 1 Department of Pathology, University Hospital, Zurich, Switzerland Periostin (POSTN) is an extracellular matrix N-glycoprotein of 93 kDa. Six different splice isoforms were reported, but only four of them sequenced.