Frequent reduction or loss of DCC gene expression in human osteosarcoma.
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.
Horstmann
M A
MA
Department of Paediatric Haematology/Oncology, University Hospital Eppendorf, Hamburg, Germany.
Pösl
M
M
Scholz
R B
RB
Anderegg
B
B
Simon
P
P
Baumgaertl
K
K
Delling
G
G
Kabisch
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D000075389:DCC Receptor; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; D017931:DNA Primers; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins