Suppression of T1-receptor expression by antisense RNA abrogates differentiation of osteogenic osteosarcoma cells.
Soluble and membrane-associated variants of the orphan T1-receptor, a homolog of interleukin-1 receptor type I, are expressed in proliferating preosteoblasts in differentiating bone. Recent evidence reveals that T1-receptor synthesis is retained in osteogenic osteosarcoma cells. Here we report that the suppression of T1-receptor expression by mouse osteosarcoma cells using a T1 -antisense expression vector results in the abrogation of the osteogenic potential of the tumor cells. T1-antisense-expressing tumor cells formed anaplastic tumors in vivo and failed to express the osteoblast-specific genes collagen type 1, alkaline phosphatase, and osteocalcin when cultured in a 3-dimensional collagen type I matrix in vitro. Suppression of T1-receptor synthesis did not affect the expression of the essential bone cell-specific transcription factor AML3/CBFA1 in the osteosarcoma cells. These data provide the first evidence that T1-receptor plays a key role in osteogenic differentiation.
Werenskiold
A K
AK
Institut für Pathologie, Technische Universität, München, Germany.
Schmidt
J
J
Rupp
B
B
Gössner
W
W
Höfler
H
H
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins; D010012:Osteogenesis / Q000187:drug effects*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D016372:RNA, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D050659:Core Binding Factor Alpha 1 Subunit; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D014157:Transcription Factors