Differential expression of aggrecan mRNA isoforms by chondrosarcoma cells.
BACKGROUND
Aggrecan, the large aggregating proteoglycan, is a major component of the cartilage extracellular matrix. The C-terminal globular domain (G3) of the aggrecan molecule exhibits a pattern of alternative splicing that involves three exons. Each corresponds to a subdomain, epidermal growth factor 1(EGF1), EGF2, and a short complement repeat (SCR).


METHODS
In the present study, we compared aggrecan mRNA splicing variants in osteochondrogenic tumor cells and normal cartilage using RT-PCR.


RESULTS
Normal cartilage expressed two mRNA isoforms, both containing the SCR exon, but with or without the EGF1 exon. Benign cartilaginous tumors showed the same splicing pattern as normal cartilage. However, malignant chondrosarcomas expressed additional splicing isoforms, one of which lacked all three alternative exons and another with EGF2 and SCR exons. The human chondrosarcoma cell line (Ch-1 cells) expressed further isoforms, one containing either EGF1 or EGF2 exon only, and another with all the variant exons.


CONCLUSIONS
These results imply that a change in the pattern of alternative aggrecan mRNA splicing is associated with malignant transformation of chondrocytes.
Matsui
Yoshito
Y
Department of Orthopaedic Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. ymatsui@sb4.so-net.ne.jp
Araki
Nobuhito
N
Tsuboi
Hideki
H
Tsumaki
Noriyuki
N
Nakata
Ken
K
Kawabata
Hidehiko
H
Eyre
David R
DR
Yoshikawa
Hideki
H
D053674:Aggrecans; D017398:Alternative Splicing; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002356:Cartilage / Q000378:metabolism / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000235:genetics; D016326:Extracellular Matrix Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D037181:Lectins, C-Type; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D020033:Protein Isoforms; D011509:Proteoglycans; D012333:RNA, Messenger; D004815:Epidermal Growth Factor