Abstract
The 'deleted in colon carcinoma' (DCC) gene has been considered a candidate tumour-suppressor gene that encodes for a transmembrane protein with strong structural similarity to members of the superfamily of neural cell adhesion molecules. It has been mapped to the chromosomal region 18q21.1 and it is implicated in cellular differentiation and developmental processes. In human osteosarcoma allelic loss frequently occurs on the long arm of chromosome 18, suggesting a possible involvement of the DCC gene in the pathogenesis of this tumour entity. In the present study the mRNA and protein expression and rearrangements at the DNA level of the DCC gene were addressed in 25 osteosarcomas and several tumour cell lines, including osteosarcoma- and colon carcinoma-derived cell lines. Using an reverse transcriptase polymerase chain reach in (RT-PCR)-based approach DCC expression was found to be lost or substantially reduced in 14 of 19 high-grade osteosarcomas, in three of six lower grade osteosarcomas and most of the tumour cell lines, in contrast to normally differentiated osteoblasts. Immunohistochemical studies on DCC protein expression of 14 selected tumours correlated well with the RT-PCR-based results. In view of the putative tumour-suppressor characteristics of the DCC gene its loss or reduction of expression could be a specific event in the development or progression of many high-grade osteosarcomas.
Highlights
A sensitive reverse transcriphase polymerase chain reach in (RT-PCR)-based approach was chosen to amplify deleted in colon carcinoma (DCC) transcripts from cDNA to evaluate the level of DCC gene expression
The analysis of DCC specific RT-PCR products by gel electrophoresis is demonstrated in Figure 2A and B), which presents a selection of osteosarcomas and tumour cell lines
Most of the cell lines investigated in this study demonstrated very low or even absent DCC expression, that is TE 85, Wo-OS, Saos-2, U2-OS, A-204, SW 403, SW 948, SW 11 16, HCT 116 and CCRFCEM
Summary
Twenty-five human osteosarcomas were obtained from 22 patients who underwent surgery at the University Clinic HamburgEppendorf or associated treatment centres of the Cooperative Osteosarcoma Study Group (Winkler et al, 1988). The selection of Presented in part at the AACR meeting 'Cancer- the interface between basic and applied research', Baltimore, 5-8 November 1995. Diagnosis (years) Primary tumour Specimen Femur p Femur m (lung) NE m (spine) Tibia p
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