Cloning, Mapping, and Expression Analysis of a Gene Encoding a Novel Mammalian EGF-Related Protein (SCUBE1)

Grimmond, Sean M.; Larder, Rachel; Hateren, Nick Van; Siggers, Pam; Hulsebos, Theo J.M.; Arkell, Ruth M.; Greenfield, Andy

doi:10.1006/geno.2000.6370

Cited by 82 publications

(87 citation statements)

References 33 publications

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“…Loss of expression of members of this family of proteins has been observed in a number of tumour types, including QPCT itself in melanoma (Muthusamy et al, 2006) and phaeochromocytomas (Thoue¨nnon et al, 2007). SCUBE (Signal peptide CUB EGF-like domain-containing protein) genes encode a small group of secreted plasma membrane-associated proteins characterised by an N-terminal signal peptide sequence, multiple EGF (epidermal growth factor) domains, a large spacer region containing multiple N-linked glycosylation sites and a C-terminal CUB (Complement subcomponent C1r/C1s EGF-related sea Urchin protein, Bone morphogenetic protein1) domain (Grimmond et al, 2000). Little is known about SCUBE3; however, it is plausible to suggest that it may have an antitumourigenic role, in a similar manner to proteins such as gremlin (Morris et al, 2010), in maintaining correct TGFb signalling.…”

Section: Ct Bstu1mentioning

confidence: 99%

Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma

et al. 2010

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The detection of promoter region hypermethylation and transcriptional silencing has facilitated the identification of candidate renal cell carcinoma (RCC) tumour suppressor genes (TSGs). We have used a genome-wide strategy (methylated DNA immunoprecipitation (MeDIP) and whole-genome array analysis in combination with highdensity expression array analysis) to identify genes that are frequently methylated and silenced in RCC. MeDIP analysis on 9 RCC tumours and 3 non-malignant normal kidney tissue samples was performed, and an initial shortlist of 56 candidate genes that were methylated by array analysis was further investigated; 9 genes were confirmed to show frequent promoter region methylation in primary RCC tumour samples (KLHL35 (39%), QPCT (19%), SCUBE3 (19%), ZSCAN18 (32%), CCDC8 (35%), FBN2 (34%), ATP5G2 (36%), PCDH8 (58%) and CORO6 (22%)). RNAi knockdown for KLHL35, QPCT, SCUBE3, ZSCAN18, CCDC8 and FBN2 resulted in an anchorage-independent growth advantage. Tumour methylation of SCUBE3 was associated with a significantly increased risk of cancer death or relapse (P ¼ 0.0046). The identification of candidate epigenetically inactivated RCC TSGs provides new insights into renal tumourigenesis.

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Section: Ct Bstu1mentioning

confidence: 99%

Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma

et al. 2010

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“…2C and 4), a tetraspanin molecule that associates with integrins to control lamellipodia formation (22); Numb (4.3-fold, Table I), a component of the Drosophila planar polarity signaling that regulates epithelial cell polarity (23); and Tmod3, (Tropomodulin-3) (4-fold, Table I), an actin filament pointed end-capping protein that, in excess, inhibits lamellipodia protrusion and cell motility (24); and Vnn1 (Vanin-1) (9.8-fold, Fig. 2H), which encodes a GPI-anchored protein possibly implicated in cell migration in the thymus and in mammalian sexual development (25,26).…”

Section: Fgf10 Induces Genes That Regulate Cell Polarity Adhesion Amentioning

confidence: 99%

Identification of FGF10 Targets in the Embryonic Lung Epithelium during Bud Morphogenesis

Lü

Izvolsky

Qian

et al. 2005

Journal of Biological Chemistry

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Genetic studies implicate Fgf10-Fgfr2 signaling as a critical regulator of bud morphogenesis in the embryo. However, little is known about the transcriptional targets of Fgf10 during this process. Here we identified global changes in gene expression in lung epithelial explants undergoing FGF10-mediated budding in the absence of other growth factors and mesenchyme. Targets were confirmed by their localization at sites where endogenous Fgf10 signaling is active in embryonic lungs and by demonstrating their induction in intact lungs in response to local application of FGF10 protein. We show that the initial stages of budding are characterized by marked up-regulation of genes associated with cell rearrangement and cell migration, inflammatory process, and lipid metabolism but not cell proliferation. We also found that some genes implicated in tumor invasion and metastatic behavior are epithelial targets of Fgf10 in the lung and other developing organs that depend on Fgf10-Fgfr2 signaling to properly form. Our approach identifies Fgf10 targets that are common to multiple biological processes and provides insights into potential mechanisms by which Fgf signaling regulates epithelial cell behavior.Signaling by fibroblast growth factor 10 (Fgf10) 1 and its receptor Fgfr2b is critical for bud morphogenesis in many developing structures. During organogenesis, Fgf10 is expressed by the mesoderm from where it diffuses to activate Fgfr2b in adjacent endodermal or ectodermal-derived cells and induce budding (1). Disruption of Fgf10-Fgfr2b signaling is lethal at birth and results in multiple organ defects. Abnormalities in Fgf10-or Fgfr2b-deficient mice include agenesis of the anterior pituitary gland, lung, thyroid, salivary gland, and limb and dysgenesis of inner ear, teeth, skin, pancreas, kidney, palate, and hair follicles (2-5). Fgf10 expression is also required for adipocyte differentiation and wound healing (6 -8).In the developing respiratory tract of the mouse, Fgf10 is first detected at embryonic (E) day 9.5 during primary bud formation. Subsequently, during branching morphogenesis (E10.5-16.5), Fgf10 is dynamically expressed in the distal lung mesenchyme at the prospective sites of budding (9, 10). The spatial and temporal distribution of Fgf10 is essential for patterning of lung epithelial tubules.Bud morphogenesis involves major changes in cytoskeletal organization, cell adhesion, migration, invasion, and proliferation among other activities. Little is known about the targets of Fgf10-Fgfr2b signaling in the lung epithelium when buds are forming. Although gene expression in the developing lung has been characterized by several reports, most studies were performed in the intact organ. Using whole lungs to identify targets that result primarily from Fgf10-Fgfr2b activation is difficult, because in the mesoderm, Fgf10 is present with several other endogenous signals such as Wnts, hepatocyte growth factor, or epidermal growth factor.Previous studies have shown that recombinant FGF10 is able to support bud morphogenesi...

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“…In the case of the human HEK293 expression profiling, temporal profiles were generated by comparing multiple time points after induction with doxycycline to a common reference RNA (parental HEK293 cell line). In all, 40 mg of RNA from the test and reference samples was reverse transcribed in the presence of Cy3-dUTP or Cy5-dUTP, respectively (Amersham), as previously described (Grimmond et al, 2000). These samples were then pooled and cohybridized to OCI human 19 K 2.2 arrays, containing approximately 19 008 double-spotted cDNAs.…”

Section: Expression Profilingmentioning

confidence: 99%

“…While more commonly exploited in the analysis of cancer biology, expression profiling is also proving valuable in the dissection of developmental processes, including sex determination (Grimmond et al, 2000). Expression profiling has been applied to WT1 biology both to investigate the validity of previously proposed WT1 targets, and to identify additional physiological targets.…”

Section: Introductionmentioning

confidence: 99%

Anlaysis of complementary expression profiles following WT1 induction versus repression reveals the cholesterol/fatty acid synthetic pathways as a possible major target of WT1

et al. 2004

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Cloning, Mapping, and Expression Analysis of a Gene Encoding a Novel Mammalian EGF-Related Protein (SCUBE1)

Cited by 82 publications

References 33 publications

Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma

Genome-wide methylation analysis identifies epigenetically inactivated candidate tumour suppressor genes in renal cell carcinoma

Identification of FGF10 Targets in the Embryonic Lung Epithelium during Bud Morphogenesis

Anlaysis of complementary expression profiles following WT1 induction versus repression reveals the cholesterol/fatty acid synthetic pathways as a possible major target of WT1

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