%0 Journal Article
%T Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways
%A Emanuele Marra
%A Paolo Uva
%A Valentina Viti
%A Valeria Simonelli
%A Eugenia Dogliotti
%A Emanuele De Rinaldis
%A Armin Lahm
%A Nicola La Monica
%A Alfredo Nicosia
%A Gennaro Ciliberto
%A Fabio Palombo
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-129
%X A bladder cell line was engineered to express a doxycycline (dox) regulated shRNA against PSCA. To shed light on the PSCA biological role in tumor growth, microarray analysis was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCRDown regulation of the PSCA expression was associated with reduced cell proliferation in vitro and in vivo. Mice bearing subcutaneous tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway analysis of deregulated genes suggests a statistical significant association between PSCA downregulation and activation of genes downstream of the IFN¦Á/¦Â receptor.These experiments established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response.PSCA has been discovered a decade ago and has been classified as a member of the Ly-6 family of GPI-anchored cell surface proteins [1]. It is expressed in most prostate cancer specimens, including high-grade prostatic intraepithelial neoplasia, primary androgen-dependent tumors, and hormone-refractory metastases. PSCA levels are positively correlated with Gleason grade, tumor stage, and biochemical recurrence. Its expression is also particularly elevated in bone metastasis. Finally, PSCA is strongly expressed in other malignancies, including bladder and pancreatic cancers [2-6]. Different immunotherapy approaches targeting PSCA have been tested in preclinical models including cancer vaccine, therapeutic monoclonal antibodies and antibody conjugated to toxic drugs [7-10]. More recently, a human monoclonal antibody targeting PSCA has been evaluated in a phase I clinical trial in prostate cancer patients (AACR 2006).Little information is available regarding the biological role of PSCA. Proteins belonging to the Ly6 family are involved in cell signaling events associa
%U http://www.biomedcentral.com/1471-2407/10/129