Osteopontin (OPN) is a soluble secreted phosphoprotein that binds with high affinity to several different integrins. While numerous activities have been ascribed to OPN in vitro, and several in vivo functions have been suggested for the molecule, including much attention focused recently on OPN in different pathologies, the actual role that the protein plays in mammalian physiology remains conjectural. Analysis of recently developed strains of mice lacking OPN because of a targeted disruption of its gene promises to provide important information on this issue. Here, we review the data implicating OPN as functioning in a variety of pathologic conditions as well as the initial results generated with the OPN knockout mice, with particular focus on the question of whether OPN has a protective or a damaging effect in different pathologies. These data will be important to the definition of how OPN contributes to mammalian physiology and pathophysiology.

Animals↗

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Induction of expression of osteopontin (OPN; secreted phosphoprotein) in metastatic, ras-transformed NIH 3T3 cells.

We have previously shown that transfection of NIH 3T3 cells with the T24 H-ras oncogene converts the cells to a tumorigenic and metastatic phenotype, in proportion to levels of ras expression. We hypothesize that ras-induced increases in malignancy occur via altered expression of various genes. We have identified OPN (osteopontin; also known as Secreted Phosphoprotein, 2ar, Eta-1, and transformation-associated phosphoprotein) as a ras-induced gene in these cells. We report here that expression of OPN RNA and secretion of OPN protein are increased in a series of ras-transformed NIH 3T3 cells, in proportion to levels of expression of ras. Detection of secreted OPN protein was facilitated by a barium citrate precipitation procedure. Although the function of this protein in tumor cells is not known, OPN contains a conserved GRGDS (glycine-arginine-glycine-aspartic acid-serine) amino acid sequence, which may function as a cell attachment site for this protein. We speculate that increased expression of OPN contributes to the increased malignancy of ras oncogene-transformed NIH 3T3 cells, perhaps by alterations in either adhesive properties or integrin-mediated signal transduction pathways.

3T3 Cells↗

PubMedDate not supplied

On the use of anti-sense RNA: down-regulation of mRNA encoding a metalloproteinase inhibitor.

In this article we describe methods used for producing anti-sense RNA and the mechanisms by which specific eukaryotic gene functions are inhibited. We also describe some of our studies with plasmid constructs producing anti-sense RNA targeted to a murine metalloproteinase inhibitor and review the evidence for naturally occuring anti-sense transcripts in eukaryotes.

Animals↗