DBC1 re-expression alters the expression of multiple components of the plasminogen pathway

Abstract

Deleted in bladder cancer 1 (DBC1) is a candidate gene for the bladder tumour suppressor locus at 9q33.1. The function of the gene is currently unknown but a crossspecies sequence comparison suggests an important role, as it is highly evolutionarily conserved. Here, we transfected a nonexpressing human bladder cancer cell line with a set of human DBC1 cDNA constructs. The effect on global expression patterns was assessed using cDNA microarrays. The cell clone with the lowest level of DBC1 expression showed induced expression of 26 genes including plasminogen activator inhibitor 2 (SERPINB5; 4.6-fold), heparin-binding EGF-like growth factor precursor (DTR; 4.2-fold), small proline-rich protein 2B (SPRR2B; 3.6-fold), metallothionein 1 isoforms (MT1B/ MT1A/MT-1F; from 2.9-to 3.2-fold), tissue-type plasminogen activator precursor (PLAT; 2.8-fold) and urokinase-type plasminogen activator precursor (PLAU; 2.7-fold). In clustering analysis, both PLAT and PLAU clustered with the functionally related urokinase plasminogen activator surface receptor (PLAUR; 1.9-fold). Furthermore, 14 human bladder tumours were analysed by real-time quantitative PCR using gene-specific primers for selected (n ¼ 20) genes. The expression levels of SERPINB5, PLAU, PLAUR and MT1 correlated with the DBC1 levels, suggesting previously unknown involvement of DBC1 in the urokinase-plasminogen pathway.

Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC

“…It is of note that 21 tumour-suppressor genes map within either the specific or the consistently altered regions. TIMP3 and PTEN have already been reported as tumour suppressors in thyroid tumours (Hu et al, 2006;Hou et al, 2007;Wang et al, 2007), while others are involved in a variety of different tumour types, for example, TGFBR3 and ANXA7 in prostate cancer (Torosyan et al, 2006;Dong et al, 2007), TNFSF15 and TUSC1 in lung cancer (Shan et al, 2004;Hou et al, 2005), SYK and Net1 in breast cancer (Repana et al, 2006;Huang et al, 2007), SLIT1, RSU1 and KLF6 in gliomas and glioblastosmas (Chunduru et al, 2002;Dickinson et al, 2004;Camacho-Vanegas et al, 2007), DBC1 in bladder cancer (Louhelainen et al, 2006), DEC1 in oesophageal squamous cell carcinomas (Yang et al, 2005), RB1 in retinoblastoma (Corson and Gallie, 2007) and LATS2 and DLEU7 in leukaemias (Hammarsund et al, 2004;Jimenez-Velasco et al, 2005). Some of these tumour suppressors have influence on the regulation of chromatin acetylation …”

Molecular pathogenesis of bladder cancer

“…[18][19][20] Re-expression in tumor cells with HD is inhibitory, pointing to a tumor suppressor role. 21 However, the function of the gene is unknown and further studies are needed to unambiguously confi rm this as a bona fi de bladder tumor suppressor.…”

Gene expression profile and enrichment pathways in different stages of bladder cancer

“…Superficial tumors are characterized by gainof-function mutations affecting oncogenes such as HRAS (Burchill et al, 1994), FGFR3 (van Rhijn et al, 2001), and PIK3CA (López-Knowles et al, 2006). In addition, candidate suppressor genes mapping to the long arm of chromosome 9, such as TSC1 (Hornigold et al, 1999), PTCH (McGarvey et al, 1998), DBC1 (Louhelainen et al, 2006), and INK4A (Orlow et al, 1999), also appear to be involved, at least in the initiation of certain papillary non-invasive neoplasms. In contrast, invasive tumors are associated with loss-of-function mutations, affecting tumor suppressor genes such as Tp53, RB (Castillo-Martin et al, 2010), and PTEN (Han et al, 2008).…”