== -Catenin transfection and siRNA knockdown affect Rac1 activity. Gemcabene calcium of the biological behavior of astrocytoma cells. == Background == Astrocytoma arises from neural stem or progenitor cells in the central nervous system. It is the most common primary brain tumor and accounts for approximately 60% of all brain tumors. Despite combined treatment strategies, which include surgery, radiotherapy and chemotherapy, the prognosis for high-grade astrocytoma, especially glioblastoma multiforme, has changed little over the past 10 years, with a median survival of only approximately 1 year [1]. The clinical symptoms and prognosis are closely correlated with tumor location and size and histological grade. Although the histological grade partly reflects the malignant features of astrocytoma, it cannot give an indication of the exact mechanism of tumor invasion and recurrence [2,3]. Thus, it is important to understand the molecular mechanism of astrocytoma cell invasion and identify effective markers in tumorigenesis and progression. The expression of -catenin was initially found to be limited to brain neurons and it can bind to presenilin 1, which is involved in the progression of Alzheimer’s disease [4-6]. -Catenin was also implicated in the maintenance of synaptic function and transmission of downstream signals as a scaffold protein [7-11]. It was reported that -catenin overexpression changed the morphology of MDCK cells, including the elaboration of lamellipodia [12]. Furthermore, -catenin can regulate the activity of small GTPases and therefore induces dendritic protrusions from cells [13]. Small GTPases are critical mediators of cytoskeletal reorganization, signal transduction and gene expression pathways [14,15]. As one of these GTPases, Rac1 is a pleiotropic regulator of many cellular processes, including the cell cycle, cell-cell adhesion, motility (through the actin network) and epithelial differentiation. -Catenin Gemcabene calcium also affects invasion and metastasis of lung cancer cells via regulation of small GTPase activity [16]. These studies suggest that -catenin plays an important role in many human cancers. Our previous study showed that -catenin was overexpressed in non-small-cell lung cancer and enhanced cancer cell invasion through small GTPase regulation. However, the expression pattern of -catenin in glial cells and human astrocytoma cells is not clear; the relationship between its expression and clinicopathological factors and biological behavior still needs to be addressed. In the present study, we examined the expression of -catenin in 156 astrocytoma tissue specimens and analyzed the correlation between its expression and clinicopathological factors. We also investigated the effect of -catenin on Rac1 activity and the biological behavior of astrocytoma cell lines. == Methods == == Patients and specimens == The study protocol was approved by the institutional review board of China Medical Gemcabene calcium University. Primary tumor specimens and adjacent normal brain tissue were obtained from 156 patients diagnosed with astrocytoma who underwent resection in the First Affiliated Hospital of China Medical University between 2005 and 2008. None of the patients had received radiotherapy or chemotherapy before surgical resection. There were 95 male (60.9%) and 61 female (39.1%) patients with a median age of 43 years (range 15-67 years). The histological diagnosis and differentiation grade were evaluated for sections stained with hematoxylin and eosin according to the World Health Organization (WHO) classification guidelines. All 156 specimens were re-evaluated with respect to histological subtype and tumor grade. Tumors were graded and classified into grade I (11), grade II (61), grade III (51), and grade IV (33) according to WHO guidelines (2007). == Cell culture and transfection == U251 and U87 cell lines were obtained from American Type Culture Gemcabene calcium Collection (Manassas, VA, USA). The cells were cultured in DMEM (Invitrogen, Carlsbad, CA, USA) containing 10% fetal calf serum (Invitrogen), 100 IU/ml penicillin (Sigma, St. Louis, MO, BSPI USA), and 100 g/ml streptomycin (Sigma). Cells were grown on sterilized culture dishes and were passaged every 2 days with 0.25% trypsin (Invitrogen). The pCMV5-FLAG/-catenin.