Molecular analysis of transitional cell carcinoma using cDNA microarray

Mor, Orna; Nativ, Ofer; Stein, Avi; Novak, Lion; Lehavi, Dana; Shiboleth, Yoel Moshe; Rozen, Ada; Berent, Eva; Brodsky, Leonid; Feinstein, Elena; Rahav, Ayelet; Morag, Keren; Rothenstein, Daniel; Persi, Nurit; Mor, Yoram; Skaliter, Rami; Regev, Aviv

doi:10.1038/sj.onc.1207039

Cited by 42 publications

(30 citation statements)

References 40 publications

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“…Cytoskeletal rearrangements seem to be an early change in the neoplastic process of the urothelium (Southgate et al, 1999;Mor et al, 2003;Sanchez-Carbayo et al, 2003). Consistent with the literature, we found members of the cytokeration family, especially KRT7, but also KRT8 highly expressed in Ta tumours (Southgate et al, 1999;Mor et al, 2003).…”

Section: Discussionsupporting

confidence: 88%

“…Of particular interest is the SDC1 gene (Barbareschi et al, 2003;Mor et al, 2003), which in breast cancer is expressed at high levels, and is related to an aggressive phenotype, and poor clinical behavior (Barbareschi et al, 2003). The SDC1 transcript encodes a transmembrane heparan sulfate proteoglycan, which acts as a receptor of the extracellular matrix and thereby is involved in cell -cell adhesion, organisation of cell -matrix adhesion, and regulation of growth factor signalling.…”

Section: Discussionmentioning

confidence: 99%

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Gene expression profiling of noninvasive primary urothelial tumours using microarrays

et al. 2005

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At present, the mechanism leading to bladder cancer is still poorly understood, and our knowledge about early events in tumorigenesis is limited. This study describes the changes in gene expression occurring during the neoplastic transition from normal bladder urothelium to primary Ta tumours. Using DNA microarrays, we identified novel differentially expressed genes in Ta tumours compared to normal bladder, and genes that were altered in high-grade tumours. Among the mostly changed genes between normal bladder and Ta tumours, we found genes related to the cytoskeleton (keratin 7 and syndecan 1), and transcription (high mobility group AT-hook 1). Altered genes in high-grade tumours were related to cell cycle (cyclin-dependent kinase 4) and transcription (jun d proto-oncogene). Furthermore, we showed the presence of high keratin 7 transcript expression in bladder cancer, and Western blotting analysis revealed three major molecular isoforms of keratin 7 in the tissues. These could be detected in urine sediments from bladder tumour patients.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Gene expression profiling of noninvasive primary urothelial tumours using microarrays

et al. 2005

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“…44,45 Evidence is emerging that members of the Rab superfamily of proteins may play important roles in cancer progression. 46 For example, increased Rab25 protein levels have been observed in prostate cancer, 47 transitional cell carcinoma of the bladder, 48 ovarian 49 and breast cancer. 49,50 In addition, overexpression of Rab25 in ovarian and breast cancer cell lines increases survival, without affecting cell-cycle progression as determined by PI staining, whereas Rab25 gene silencing markedly increases sensitivity to apoptosis in response to a variety of stimuli.…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of Rab prenylation by a phosphonocarboxylate analogue of risedronate induces apoptosis, but not S‐phase arrest, in human myeloma cells

Roelofs¹,

Hulley²,

Meijer³

et al. 2006

Intl Journal of Cancer

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Bisphosphonates (BPs) are widely used in the treatment of osteolytic bone disease associated with multiple myeloma, and have been demonstrated to exert antitumor effects both in vitro and in vivo. However, the precise molecular mechanisms involved in the direct antitumor effects of BPs in vitro are not known. Nitrogen‐containing BPs, such as risedronate (RIS), act by inhibiting protein prenylation. A phosphonocarboxylate analogue of RIS, 3‐PEHPC, has previously been shown in osteoclasts and macrophages to specifically inhibit prenylation of Rab GTPases. The aim of this study was to identify the molecular targets of RIS and 3‐PEHPC in human myeloma cells and to determine the cellular effects of selective inhibition of Rab prenylation by 3‐PEHPC as compared to nonspecific inhibition of protein prenylation by RIS in human myeloma cells. RIS dose‐dependently inhibited prenylation of both Rap1A and Rab6, whereas 3‐PEHPC only inhibited Rab6 prenylation. Both RIS and 3‐PEHPC dose‐dependently increased apoptosis in human myeloma cells. RIS induced an accumulation of cells in the S‐phase of the cell cycle, associated with inhibition of DNA replication. In contrast, 3‐PEHPC did not cause cell‐cycle arrest. Furthermore, geranylgeraniol could prevent inhibition of prenylation, induction of apoptosis, and cell‐cycle arrest in response to RIS, but not inhibition of Rab prenylation and apoptosis induced by 3‐PEHPC, consistent with specific inhibition of Rab geranylgeranyl transferase by 3‐PEHPC. In conclusion, our studies demonstrate that selective inhibition of Rab prenylation induces apoptosis, but not S‐phase arrest, thus identifying distinct molecular pathways that mediate the antimyeloma effect of nitrogen‐containing BPs. © 2006 Wiley‐Liss, Inc.

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“…In recent years, genome-wide expression profiling by the use of microarray technology has contributed to extensive and new insights into the complex gene expression patterns and dysregulation of genes occurring in urothelial neoplasias (Thykjaer et al, 2001;Dyrskjt et al, 2003Dyrskjt et al, , 2004Dyrskjt et al, , 2005Mor et al, 2003;SanchezCarbayo et al, 2003;Modlich et al, 2004;Blaveri et al, 2005;Kim et al, 2005;Wild et al, 2005). Microarray analyses have not only delineated gene expression profiles distinct for different histological subtypes (Thykjaer et al, 2001;Dyrskjt et al, 2003Dyrskjt et al, , 2004Sanchez-Carbayo et al, 2003;Blaveri et al, 2005;Wild et al, 2005), but also gene expression signatures of importance for tumor recurrence and progression (Dyrskjt et al, 2003(Dyrskjt et al, , 2005Modlich et al, 2004;Wild et al, 2005), and patient survival (Blaveri et al, 2005;Kim et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

et al. 2006

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We used gene expression profiling, mutation analyses of FGFR3 and TP53, and LOH analyses of chromosome 9 and the TP53 region on chromosome arm 17p, to molecularly characterize 75 Ta and T1 bladder carcinomas. We identified four major cellular processes related to cell cycle, protein synthesis, immune response, and extra cellular components that contribute to the expressional heterogeneity of early-stage urothelial cell carcinoma (UCC). Activating FGFR3 mutations were found at the highest frequency in G1 tumors (80%), and showed a strong correlation with FGFR3 expression. In contrast, G3 tumors displayed mutations in less than 10% of the cases and a low level of FGFR3 expression. Even though LOH on chromosome 9 was not associated with any specific expression pattern, our data indicate that loss of chromosome 9 is associated with tumor development rather than initiation. The combined analyses suggest the existence of two types of UCC tumors, one which is characterized by FGFR3 mutation or expression, high expression of protein synthesis genes, and low expression of cell cycle genes. Furthermore, the presented data underscore FGFR3 receptor involvement in urothelial cell transformation as the presence of FGFR3 mutations has a major impact on the global gene expression profile of bladder carcinomas.

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Molecular analysis of transitional cell carcinoma using cDNA microarray

Cited by 42 publications

References 40 publications

Gene expression profiling of noninvasive primary urothelial tumours using microarrays

Gene expression profiling of noninvasive primary urothelial tumours using microarrays

Selective inhibition of Rab prenylation by a phosphonocarboxylate analogue of risedronate induces apoptosis, but not S‐phase arrest, in human myeloma cells

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

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