CDO - AN ONCOGENE-REGULATED, SERUM-REGULATED, AND ANCHORAGE-REGULATEDMEMBER OF THE IG FIBRONECTIN TYPE-III REPEAT FAMILY/

Cell adhesion molecules of the Ig superfamily are implicated in a wide variety of biological processes, including cell migration, axon guida nce and fasciculation, and growth control and tumorigenesis. Expressio n of these proteins can be highly dynamic and cell type specific, but little is known of the signals that regulate such specificity. Reporte d here is the molecular cloning and characterization of rat CDO, a nov el cell surface glycoprotein of the Ig superfamily that contains five Ig-like repeats, followed by three fibronectin type III-like repeats i n its extracellular region, and a 256-amino acid intracellular region that does not resemble other known proteins. In rat embryo fibroblasts , cdo mRNA expression is maximal in confluent, quiescent cells. It is rapidly and transiently down-regulated by serum stimulation of such ce lls, and is constitutively down-regulated in oncogene-transformed deri vatives of these cells. CDO protein levels are also dramatically regul ated by cell-substratum adhesion, via a mechanism that is independent of cdo mRNA expression. The amount of CDO produced at the surface of a cell may therefore be governed by a complex balance of signals, inclu ding mitogenic stimuli that regulate cdo mRNA levels, and substratum-d erived signals that regulate CDO protein production. cdo mRNA is expre ssed at low levels in most adult rat tissues. A closely related human gene maps to chromosome 11q23-24, a region that displays frequent loss of heterozygosity in human lung, breast, and ovarian tumors. Taken to gether, these data suggest that loss of CDO function could play a role in oncogenesis.