Gene expression profiling of metastatic brain cancer

Abstract

Abstract. Gene expression profiling of metastatic brain tumors from primary lung adenocarcinoma, using a 17k-expression array, revealed that 1561 genes were consistently altered. Further functional classification placed the genes into seven categories: cell cycle and DNA damage repair, apoptosis, signal transduction molecules, transcription factors, invasion and metastasis, adhesion, and angiogenesis. Genes involved in apoptosis, such as caspase 2 (CASP2), transforming growth factor-ß inducible early gene (TIEG), and neuroprotective heat shock protein 70 (Hsp70) were underexpressed in metastatic brain tumors. Alterations in Rho GTPases (ARHGAP26, ARHGAP1), as well as down-regulation of the metastasis suppressor gene KiSS-1 were noted, which may contribute to tumor aggression. Overexpression of the invasion-related gene neurofibromatosis 1 (NF1), and angiogenesis-related genes vascular endothelial growth factor-B (VEGF-B) and placental growth factor (PGF) was also evidenced. Brain-specific angiogenesis inhibitors 1 and 3 (BAI1 and BAI3) were underexpressed as well. Examination of cell-adhesion and migration-related genes revealed an increased expression of integrins and extracellular matrices collagen and laminin. The study also showed alterations in p53 protein-associated genes, among these increased gene expression of p53, up-regulation of Reprimo or candidate mediator of the p53-dependent G2-arrest, down-regulation of p53-regulated apoptosis-inducing protein 1 (p53AIP1), decreased expression of tumor protein inducible nuclear protein 1 (p53DINP1), and down-regulation of Mdm4 (MDMX). The results demonstrated that genes involved in adhesion, motility, and angiogenesis were consistently upregulated in metastatic brain tumors, while genes involved in apoptosis, neuroprotection, and suppression of angiogenesis were markedly down-regulated, collectively making these cancer cells prone to metastasis.

Oncogenic ras-induced Down-regulation of Pro-apoptotic Protease Caspase-2 Is Required for Malignant Transformation of Intestinal Epithelial Cells

“…It is also known that caspase-2 expression is frequently reduced in human gastric tumors when compared with normal gastric mucosa (65). Furthermore, caspase-2 was found to be significantly underexpressed in metastatic brain tumors (66). Finally, caspase-2-deficient mice were demonstrated to be noticeably more susceptible to Myc-induced lymphoma than the respective wild type mice (62).…”

Inactivation of ABL kinases suppresses non–small cell lung cancer metastasis

“…Both the PC9M and M4M5 cells display enhanced metastatic activity compared with parental cells. Gene set enrichment analysis (GSEA) (18) using multiple metastasis signature gene sets (15,17,(19)(20)(21)(22) was employed to query pathways dependent on the ABL kinases. NSCLC cells knocked down for both ABL1 and ABL2 or treated with the ABL allosteric inhibitor GNF5 displayed reduced expression of metastasis gene signatures (Figure 1).…”

Distinct roles of ROCK1 and ROCK2 during development of porcine preimplantation embryos

“…Rho-associated coiled-coil protein kinases (ROCKs) are downstream targets of RhoA small GTP-binding proteins, and regulate cell adhesion, cytokinesis, cell proliferation, and apoptosis (Takai et al 1995, Narumiya et al 1997, Etienne-Manneville & Hall 2002, Riento & Ridley 2003, Zohrabian et al 2009). To date, two isoforms of ROCK, ROCK1 and ROCK2, have been described in mammalian cells , Matsui et al 1996.…”