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For rare cancers such as neuroendocrine bladder cancer treatment options are limited due partly to the lack of preclinical models. Techniques to amplify rare primary neuroendocrine bladder cancer cells could provide novel tools for the discovery of drug and diagnostic targets. We developed preclinical experimental models for neuroendocrine bladder cancer.Fresh tumor tissue from 2 patients with neuroendocrine bladder cancer was used to establish in vitro and in vivo models. We analyzed additional archived tissues in the National Center of Tumor Diseases tissue bank from patients with neuroendocrine bladder cancer. Primary tumor samples were collected during radical cystectomy. PHA-665752 was used to inhibit MET in animal models and cell cultures. The expression of markers and drug targets in neuroendocrine bladder cancer was determined by flow cytometry. The growth of neuroendocrine bladder cancer in vitro was determined by counting live cells. Tumor growth in mice was assessed by measuring tumor volume. Groups were compared using the nonparametric Kruskal-Wallis test.Xenograft models and serum-free cultures of neuroendocrine bladder cancer cells allowed screening for cell surface markers and drug targets. We found expression of the HGF receptor MET in neuroendocrine bladder cancer cultures, xenograft models and primary patient sections. The growth of neuroendocrine bladder cancer spheroids in vitro depended critically on HGF. Treatment of neuroendocrine bladder cancer bearing mice with a MET inhibitor significantly decreased tumor growth compared to that in control treated mice.Neuroendocrine bladder cancer xenografts and serum-free cultures provided suitable models in which to identify diagnostic markers and therapeutic targets. Using the models, we noted HGF dependent growth of human neuroendocrine bladder cancer and identified MET as a new treatment target for neuroendocrine bladder cancer.

and ChIP test whether AIB1 is necessary for glycolytic genes transcription. The independent statistics analysis of microarray was employed to identify the correlation between AIB1 and glycolytic genes. RESULTS: Our results demonstrated knockdown of AIB1 in bladder cancer cells induced G1 arrest and Our results demonstrated knockdown of AIB1 in bladder cancer cells induced G1 arrest and apoptosis, inhibited colony formation and tumorigenesis in vivo. Cell cycle inhibitor, p27, was up-regulated and survival protein BCL2 was reduced in AIB1 knockdown cells independence of cell type. Depletion of AIB1 by RNA interference and pharmacologic inhibition reduced glucose consumption, lactate and ATP production in T24 cancer cells under hypoxia. By interacting with HIF1 , AIB1 was required for HIF1 transcriptional activity and its glycolytic target gene expression, through direct recruitment onto promoters of HIF1 target genes. AIB1expression level showed positive correlation with glycolytic genes in clinic UCB specimen. CONCLUSIONS: Together, oveexpression of AIB1 is required for glycolysis in bladder cancer cells through HIF1 , eventually to facilitate tumorigenesis. Targeting AIB1 by gossypol may be an intriguing approach for bladder cancer therapy.

Patrick J. Bastian*, Munchen, Germany; Matthias May, Straubing, Germany; Hans-Martin Fritsche, Regensburg, Germany; Alexander Buchner, Munchen, Germany; Sabine Brookman-May, Regensburg, Germany; Christian Bolenz, Mannheim, Germany; Edwin Hermann, Munster, Germany; Maximillian Burger, Regensburg, Germany; Thomas Hofner, Heidelberg, Germany; Jorg Elliger, Bonn, Germany; Derya Tilki, Munchen, Germany; Lutz Trojan, Mannheim, Germany; Christian Wulfing, Munster, Germany; Axel Haferkamp, Frankfurt, Germany; Christian Gilfrich, Straubing, Germany; Markus Hohenfellner, Heidelberg, Germany; Wolf F. Wieland, Regensburg, Germany; Stefan C. Muller, Bonn, Germany; Philipp Nuhn, Munchen, Germany