In summary, the strong proliferation stimulating learn more function and the additional pro-angiogenic, pro-migratory and stroma-inducing characteristics of IGF-II have an important effect on tumor progression and tumor-stroma interaction. Poster No. 56 TRAF Family Member Associated NF-KB activatior (TANK) Mediates TGFbeta Resistance in Breast Cancer Mahaveer Swaroop Bhojani 1 , Rajesh Ranga1, Swathi Pasupulati1, Brian Ross1, Alnawaz Rehemtulla1

1 Radiation Oncology, University of Michigan, Ann Arbor, MI, USA TGF-beta and their receptors are key regulators of many aspects of cell growth, differentiation, and function. Regulation of TGF-beta expression and activation is crucial for normal development and growth control. The loss of responsiveness of different tumor cells to the antiproliferative

effects and a novel nexus between TGF-beta expression and increased tumorigenicity, invasion and drug resistance is a common find more feature in carcinogenesis. Here we show, by in silico meta-analysis of breast cancer microarray data that TRAF Family-Associated NF-KappaB Activator (TANK), a signaling adaptor protein reported to be involved in regulating NF-κB activity, is upregulated in metastatic breast cancer and grade 3 tumors. Further, upregulation of MM-102 TANK was seen in 67% of invasive breast cancers (n = 148) by immunohistochemistry based tissue microarray analysis and by western blotting in a number of human breast cancer cells lines. In BT474, breast cancer cells that are refractory to TGF-beta, targeted down regulation of TANK using either siRNA or shRNA lead to

increased sensitization to TGF-beta and chemotherapeutic agents. Further, disruption of SMAD2 and NF-κB transcriptional activity was monitored by promoter assay, western blotting and functional ELISAs in TANK siRNA transfected cells those when compared to non silencing siRNA or vector control. Taken together, these results suggest a link between NF-κB and TGFβ signaling and that loss of responsiveness to TGF-beta may be mediated by the over-expression of TANK. Poster No. 57 Stromal PDGFR-α Expression, in Normal Mucosa and Lymph Nodes, Predicts Prognosis in Colorectal Cancer Maja Bradic Lindh 1 , Helgi Birgisson2, Janna Paulsson1, Bengt Glimelius2, Arne Östman 1 1 Oncology-Pathology Department, Cancer Center Karolinska, Karolinska Institutet, Karolinska Sjukhuset, Stockholm, Sweden, 2 Department of Surgical Sciences, Colorectal Surgery, Akademiska Sjukhuset, Institutionen för Kirurgiska Vetenskaper, Uppsala, Sweden To characterize the prognostic significance of stromal PDGFR-alpha expression in colorectal cancer (CRC), we evaluated the expression of PDGFR-alpha using a tissue micro array (TMA) of a population-based CFRC cohort of having undergone standardized treatment. The TMA was composed of more than 300 primary tumors, more than 60 lymph node metastases and 114 samples from normal colon.