Rabbit Anti-CCNE2 monoclonal antibody, clone TE3146

Objective Dihydroartemisinin (DHA), a predominant phytoconstituent in Artemisia annua L. (a plant widely used as a traditional medicine in China), inhibits lung tumorigenesis and metastasis. However, its anticancer effect against hepatocellular carcinoma has not yet been investigated. In this study, the anti-tumor potential of DHA was evaluated in vitro against the hepatocellular carcinoma HCCLM6 cell line. Results DHA (1-100 mu M) treatment suppressed the cell proliferation in dose-dependently. In addition, expression of all genes, involved in cellular proliferation (e.g. E2F1, BCL2, PCNA, MKI67 and CCNE2) and cellular motility (e.g. DOCK1, ITGA2, VCL, MMP2, FN1), was significantly downregulated by DHA (50 and 100 mu M). Global gene expression profile identified 1731 differentially expressed genes (DEGs); among them, 211 were up-regulated and 1520 were down-regulated. Besides, the extracellular matrix (ECM)-receptor interaction, focal adhesion, regulation of actin cytoskeleton and TNF pathways were enriched by DEGs. Based on the KEGG signal pathway enrichment, the FN1 and integrin-beta 1 could be a potential target for DHA for inhibiting proliferation. The expression of FN1 and integrin-beta 1 was further analyzed by the qPCR, immunohistochemistry and Western blot assay in vitro and in vivo. The results indicated that DHA decreased the FN1 and integrin-beta 1 protein levels and interfered with PI3K-AKT signal transduction pathway. Conclusions Our findings revealed that DHA could inhibit proliferation and migration of human hepatocellular carcinoma cells targeting FN1 and ITGB1 via the PI3K-AKT pathway. Therefore, DHA might be a novel drug with a potential effect against liver tumorigenesis and metastasis.

Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell-cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observe that these processes have not become significantly disregulated in VIN. In conclusion: although VIN is still a premalignant disease, it already displays several hallmarks of cancer. (c) 2007 Wiley-Liss, Inc.