Glutathione S-transferase Pi mediates proliferation of androgen-independent prostate cancer cells

Prostate cancers generally acquire an androgen-independent growth capacity with progression, resulting in resistance to antiandrogen therapy. Therefore, identification of the genes regulated through this process may be important for understanding the mechanisms of prostate carcinogenesis. We here utilized androgen-dependent/independent transplantable tumors, newly established with the ‘transgenic rat adenocarcinoma in prostate’ (TRAP) model, to analyze their gene expression using microarrays. Among the overexpressed genes in androgen-independent prostate cancers compared with the androgen-dependent tumors, glutathione S-transferase pi (GST-pi) was included. In line with this, human prostate cancer cell lines PC3 and DU145 (androgen independent) had higher expression of GST-pi compared with LNCaP (androgen dependent) as determined by semiquantitative reverse transcription–polymerase chain reaction analysis. To investigate the roles of GST-pi expression in androgen-independent human prostate cancers, GST-pi was knocked down by a small interfering RNA (siRNA), resulting in significant decrease of the proliferation rate in the androgen-independent PC3 cell line. In vivo, administration of GST-pi siRNA–atelocollagen complex decreased GST-pi protein expression, resulting in enhanced numbers of TdT mediated dUTP-biotin nick-end labering (TUNEL)-positive apoptotic cells. These findings suggest that GST-pi might play important roles in proliferation of androgen-independent human prostate cancer cells

Prohibitins Are Required for Cancer Cell Proliferation and Adhesion

Prohibitin 1 (PHB1) is a highly conserved protein that together with its homologue prohibitin 2 (PHB2) mainly localizes to the inner mitochondrial membrane. Although it was originally identified by its ability to inhibit G1/S progression in human fibroblasts, its role as tumor suppressor is debated. To determine the function of prohibitins in maintaining cell homeostasis, we generated cancer cell lines expressing prohibitin-directed shRNAs. We show that prohibitin proteins are necessary for the proliferation of cancer cells. Down-regulation of prohibitin expression drastically reduced the rate of cell division. Furthermore, mitochondrial morphology was not affected, but loss of prohibitins did lead to the degradation of the fusion protein OPA1 and, in certain cancer cell lines, to a reduced capability to exhibit anchorage-independent growth. These cancer cells also exhibited reduced adhesion to the extracellular matrix. Taken together, these observations suggest prohibitins play a crucial role in adhesion processes in the cell and thereby sustaining cancer cell propagation and survival

Mechanical behavior of hybrid FRP composites with bolted joints

The behavior of an innovative hybrid Fibre Reinforced Polymer (FRP) composite with bolted joints was investigated. Coupons and full-size specimens were tested to determine the effect of applied bolt torque and the contribution of adhesive bonding on the load capacity and failure mode of the hybrid FRP with bolted joints. The results showed that at different levels of applied bolt torque (10, 15, 20 and 25 N-m), little friction resistance developed. A slight increase on the load capacity was however observed with increasing tightening torque. On the other hand, the bolting accompanied by adhesive bonding provided resistance against slipping. The full-size hybrid FRP girder with joints using bolts and epoxy exhibited the same strength and stiffness as the girder without joints while bolting alone resulted to a beam with only 65% of the stiffness of those without joints. Theoretical analyses were conducted and result showed a good agreement with the experimental results

Flexural behavior of hybrid FRP girder with concrete deck

An innovative hybrid composite girder is being developed in Japan consisting of carbon fiber reinforced polymer (CFRP) and glass fiber reinforced polymer (GFRP). The innovative feature of this girder is the optimum use of CFRP and GFRP in flanges to maximize structural performance while reducing the overall cost by using only GFRP in the web section. The flexural behavior of such hybrid FRP composite girders was investigated. Preliminary tests revealed that hybrid FRP girder failed due to local buckling and separation of laminates in the compression flange with the tensile strain much lower than the expected maximum strain. In view of improving its structural performance and practical application, concrete deck was provided on top of the hybrid FRP composite girder to avoid local brittle failure and to fully utilize the superior characteristics of the FRP materials. Different types of shear connection were trialed to provide composite action between the hybrid FRP girder and concrete deck. This paper will discuss the results of the experimental investigation on the combined section of concrete deck and hybrid FRP composite girder focusing mainly on issues related to the composite action of such girders