AN APPARENT AUTOCRINE MECHANISM AMPLIFIES THE DEXAMETHASONE-INDUCED 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]. 2 4p3 comprises six exons, live introns and 793 bp of 5' regulatory regi on. The transcription start point (tsp) was identified by primer exten sion. 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 induc ed the expression of 24p3 dramatically in the absence of de novo prote in synthesis. This activation was further amplified by an apparent aut ocrine mechanism. Similar results were obtained with retinoic acid. Us ing the cat reporter gene system, we have shown that the 5'-flanking r egion of 24p3 confers Dex inducibility. Furthermore, we have identifie d a 43-bp region of the 24p3 promoter required for the Dex responsiven ess. The biological implications are discussed in light of these resul ts.