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Method to control tumor progression and invasiveness

a tumor and invasiveness technology, applied in the field of biotechnology, can solve the problems of catenin-complex leading to invasion and metastasis, and achieve the effect of inducing invasion in vitro

Inactive Publication Date: 2005-04-28
ROY FRANS +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0008] A possible crosstalk between the different multiprotein complexes involving E-cadherin and catenins can form the link between cell adhesion and signaling pathways that are involved in developmental and tumorigenic processes. Here we report the cloning of hECRep1a or hNanosI, as it is a human homolog of the Drosophila gene nanos. Expression of hECRep1a is down regulated by E-cadherin expression. Surprisingly, we found that the hECRep1a protein interacts with β-catenin, plakogl

Problems solved by technology

Suppression of the E-cadherin / catenin-complex leads to invasion and metastasis.

Method used

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  • Method to control tumor progression and invasiveness
  • Method to control tumor progression and invasiveness
  • Method to control tumor progression and invasiveness

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example 1

Isolation of the Full-Length hECRep1a cDNA Encoding a Human Nanos-Related Protein, and Several Homologs in Man and Mouse

E-Cadherin-Negative Versus -Positive Breast Carcinoma Cell Line System

[0069] A matched cell line couple, basically different in E-cadherin expression, was constructed by stable transfection of the invasive E-cadherin-negative cell line MDA-MB-231 with E-cadherin cDNA. This E-cadherin-positive MDA-MB-231-derivative, designated MDA2BE5.36, shows a restored epithelial phenotype in vitro with respect to strong and homogeneous expression of the E-cadherin / catenin-complex at the cell membrane, epithelioid cell morphology, growth repression, cadherin-dependent cell-cell aggregation, and a shift from a random towards a clustered spatial cell distribution, indicative for decreased invasiveness (Nawrocki-Raby et al., 2001).

Suppression Substractive Hybridization (SHH)

[0070] We have sought to identify genes whose expression is modulated by E-cadherin expression. To this ...

example 2

Expression Studies of hECRep1

hECRep1a mRNA Expression is Repressed by E-Cadherin Expression

[0076] The hECRep1a mRNA was found to be down regulated by E-cadherin expression in a Suppression Subtractive hybridization (SSH)-analysis of the E-cadherin-negative MDA-MB-231 breast cancer cell line versus an E-cadherin-transfected derivative of this cell line, MDA2BE5.36 The effective differential expression of hECRep1a in this cell line couple was confirmed by Northern blot analysis (FIG. 5a). Downregulation of hECRep1a mRNA expression by E-cadherin expression was further consolidated in SW480 cells, in which E-cadherin expression was induced by stable transfection of Smad4 cDNA (Schwarte-Waldhoff et al., 1999). Equal amounts of total RNA of both Smad4 transfected and mock transfected SW480 cells were analyzed by Northern blotting with an hECRep1a-specific probe (FIG. 5b). Smad4 transfected clones (D1 and D14) show induced E-cadherin mRNA expression and concomitantly reduced hECRep1a mR...

example 3

Human hECRep1a is a Single-Exon Gene Mapped to Chromosomal Region 10q25.3

[0082] To investigate the genomic organization of the hECRep1 gene, a 12,650-nt genomic DNA contig, comprising the hECRep1a cDNA sequence, was subjected to an in silico analysis using the NIX tool at the UK HGMP resource centre (http: / / www.hgmp.mrc.ac.uk). The genomic contig contained 6,618 nt upstream and 1,997 nt downstream of the defined hECRep1a cDNA sequence. Based on the results of the GENSCAN analysis (Burge and Karlin, 1997), the hECRep1a gene was predicted to be a single-exon gene with an open reading frame as described above. Based on the GRAIL analysis (Xu et al., 1997), promoter elements were recognized including a TATA-box at nt position −33, a GC-box at nt position −54 and a CAAT element at nt position −278 relative to the predicted CAP-structure position (nt position 1 in the cDNA sequence). Reporter plasmids driven by different fragments of the hECRep1a promoter sequences were transiently trans...

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Abstract

Described is a method of modulating E-cadherin mediated cell adhesion. More specifically, described is the use of hECRep1a and homologues thereof to modulate and / or control tumor cell invasiveness.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application is a continuation of PCT International Patent Application No. PCT / EP03 / 01683, filed on Feb. 18, 2003, designating the United States of America, and published, in English, as PCT International Publication No. WO 03 / 070759 on Aug. 28, 2003, the contents of the entirety of which is incorporated by this reference.TECHNICAL FIELD [0002] The present invention relates generally to biotechnology, and more particularly to methods modulating the E-cadherin mediated cell adhesion. More specifically, the invention relates to the use of hECRep1a and homologues thereof to modulate and / or control tumor progression and tumor cell invasiveness. Moreover, the present invention identifies hECRep1a and homologues as targets for therapy directed against human tumors, more particularly malignant tumors. BACKGROUND [0003] E-cadherin is a transmembrane molecule that forms a protein complex with cytoplasmic catenins in the zonula adherens of epi...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K48/00C12Q1/68G01N33/50G01N33/574
CPCA61K38/1709A61K48/00C07K16/2896C07K2316/96G01N2333/705C12Q2600/112C12Q2600/136G01N33/5011G01N33/57484C12Q1/6886C07K2317/76
Inventor ROY, FRANSBERX, GEERTSTRUMANE, KRISTIN
Owner ROY FRANS
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