Abstract 5110: RNA helicase p68 is a new marker for breast cancer heterogeneity

Abstract

Abstract Two major challenges in diagnosis and therapy of breast cancer lie in its heterogeneity and drug resistance. RNA helicase p68 (DDX5) has been shown to be involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator. However, its functional role in breast cancer remains elusive. We utilized an integrative biology approach strategy to further define the role of p68 in breast cancer. Specifically, we determined the expression pattern of p68 at both mRNA and protein levels for a panel of ∼50 breast cancer cell lines. We performed immunohistochemistry of p68 using tissue microarrays containing a total of over 200 cases of primary human malignant breast cancer (various grades and stages). We knocked down p68 in a panel of representative breast cancer cell lines (e.g., SKBR3 and MDA-MB-231) and investigated the functional consequences such as their proliferation and responses to Lapatinib after the p68 knockdown. Finally, we carried out SILAC-based proteomic profiling of these breast cancer cells after p68 knockdown and identified p68-targeted proteins and networks contributing to the drug responses. We found that p68 expression pattern is distinct among different subtypes of breast cancers. More aggressive basal subtypes have predominantly high p68 protein expression while low p68 expression is predominantly associated with the luminal subtype. Knockdown of p68 inhibits the proliferation of breast cancer cells and sensitizes them to cancer drugs such as Lapatinib. We demonstrated that p68 is a new marker for breast cancer heterogeneity in addition to ER, PR, and Her2. Importantly, we identified p68-regualted cytoskeletal reorganization as a new mechanism in controlling breast cancer proliferation and drug resistance. In summary, RNA helicase p68 may serve as a new marker for breast cancer heterogeneity, as a predictor for drug resistance, and as a target for a combinational therapy to circumvent drug resistance of aggressive tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5110. doi:10.1158/1538-7445.AM2011-5110