Myd88 may contribute in several ways to progression of murine mammary carcinoma (P2077)

Abstract

Abstract Previously we reported that Myd88 contributed to growth, metastasis, and expression of CCL2 and CCL5 by mammary carcinoma implying that constitutive signaling through Myd88 contributes to tumor progression. To begin to decipher downstream effects of Myd88 signaling in the tumor cells we used RNA interference and a Myd88 inhibitory peptide and then screened for expression of genes involved in signaling and the cell cycle. Some of the alterations that were found included TLR signaling components such as Tirap, Tollip, Irak1 and Irak2 suggesting a potential feedback mechanism for Myd88 in TLR signaling in the tumor cells. Many of the genes that were modulated upon Myd88 inhibition may contribute to multiple downstream effects such as inflammation, migration and growth. For instance, genes utilized for the NFKb and MAPK pathways including NF-KB1, IKB-beta, MEK, JNK and p38 exhibited reduced expression upon Myd88 inhibition. Genes encoding proteins that could regulate the cell cycle such as p53, cyclins B, D, and F were also modulated, and a role for Myd88 in cell cycle progression was confirmed by cell cycle analysis which showed that Myd88 was important for progression to the G2 phase of the cell cycle. Collectively, these data imply that Myd88 may contribute to tumor progression by regulating several pathways (apoptosis, proliferation, migration and/or inflammation), and underscores the importance of delineating the role of Myd88 in murine mammary carcinoma.