An apparent autocrine mechanism amplifies the dexamethasone- and retinoic acid-induced expression of mouse lipocalin-encoding gene 24p3

We have isolated, sequenced and characterized the mouse 24p3 gene. The 24p3 protein is a member of the lipocalin family comprising secreted transporters of hydrophobic ligands. The 24p3 cDNA had been initially isolated during a search for genes overexpressed during a SV40-induced mitotic reaction [Hraba-Renevey et al., Oncogene 4 (1989) 601-608]. 24p3 comprises six exons, live introns and 793 bp of 5' regulatory region. The transcription start point (tsp) was identified by primer extension. Putative regulatory elements, including a TATA-like box and two glucocorticoid responsive core elements (GRE), have been mapped in the S-flanking region. Based on this observation, we examined the effect of a glucocorticoid (dexamethasone, Dex) on 24p3 expression. Dex induced the expression of 24p3 dramatically in the absence of de novo protein synthesis. This activation was further amplified by an apparent autocrine mechanism. Similar results were obtained with retinoic acid. Using the cat reporter gene system, we have shown that the 5'-flanking region of 24p3 confers Dex inducibility. Furthermore, we have identified a 43-bp region of the 24p3 promoter required for the Dex responsiveness. The biological implications are discussed in light of these results.