MAP3K7 (Phospho-Ser439) ELISA Kit

A panel of kinases whose inhibition increased apoptosis of pancreatic adenocarcinoma cells in vitro was recently established. The aim of this work was to observe in a mouse xenograft model whether inhibition of these kinases would alter pancreatic tumor growth. Rate of apoptosis, caspase-3 activity and cell viability were assessed in two pancreatic cancer cell lines, MiaPaCa2 and BxPC3, after inhibiting selected kinases by transfection of specific siRNAs. For in vivo experiments, MiaPaCa2 cells were injected into the pancreas of nude mice, where they formed tumors. Inhibition of kinases was obtained by repeated intraperitoneal (i.p.) injections of modified O-Methyl (OMe) siRNAs specific for the selected kinases. Tumor volumes were assessed after 21 days. Among selected kinases, PAK7, MAP3K7 and CK2 alpha were those whose inhibition increased apoptosis the most in vitro. Simultaneous inhibition of two of them increased apoptosis up to five times. Moreover, inhibiting these kinases had little effect on 10 non-pancreatic cell lines, suggesting pancreatic specificity. In vivo, OMe-siRNAs induced significant but incomplete inhibition of kinase expression (45-75%). Nevertheless, such inhibition resulted in a twofold increase in caspase-3 activity in tumors and a strong reduction in tumor volume (about 75%). In vivo inhibition by OMe-siRNAs of three survival kinases apparently specific for pancreatic cancer cells, PAK7, MAP3K7 and CK2a, decreases significantly the growth of xenografted MiaPaCa2 cells. This strategy is therefore of potential clinical interest. Cancer Gene Therapy (2009) 16, 731-740; doi:10.1038/cgt.2009.22; published online 10 April 2009

Background Prognosis of hepatocellular carcinoma (HCC) remains poor due to high recurrence rate and ineffective treatment options, highlighting the need to better understand the mechanism of recurrence and metastasis in HCC. Methods We first collected messenger RNA (mRNA) expression data from 442 cases of HCC patients from The Cancer Genome Atlas (TCGA) database as well as 251 HCC patients from Zhongshan Hospital during 2009 and 2010 to analyze the expression pattern from tissue microarray (TMA) of baculoviral IAP repeat containing 3 (BIRC3). Then, we used BIRC3 gain-of-function (overexpression) and loss-of-function (knockdown) studies to examine the effect of BIRC3 on HCC cell proliferation and invasion. In addition, we also investigated the undying mechanism by which BIRC3 contributes to HCC tumor progression. Functionally, we also used a BIRC3-specific inhibitor AT-406 in HCC xenograft model to explore the potential therapeutic benefit of targeting BIRC3 in liver cancer. Results BIRC3 serves as a novel prognostic indicator for HCC patients undergoing curative resection. BIRC3 promotes HCC epithelial-mesenchymal transition (EMT), cell migration, and metastasis via upregulating MAP3K7, therefore, inducing ERK1/2 phosphorylation. The specific BIRC3 inhibitor AT-406 can inhibit HCC cell proliferation and reduce pulmonary metastases. Conclusion BIRC3 induces tumor proliferation and metastasis in vitro and in vivo. BIRC3 may serve as a novel therapeutic target for liver cancer.