IDENTIFICATION OF PRG1, A NOVEL PROGESTIN-RESPONSIVE GENE WITH SEQUENCE HOMOLOGY TO 6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE-2,6-BISPHOSPHATASE/

To define early molecular targets of progestin action, the differentia l display technique was used to identify genes with altered levels of expression in T-47D breast cancer cells treated with the synthetic pro gestin ORG 2058 for 3 h. PRG1 was first isolated as a 200-bp cDNA clon e and its progestin regulation confirmed by Northern analysis. Cloning of the complete coding region of PRG1 revealed that it shared a high degree of amino acid sequence identity with isoforms of the enzyme pho sphofructo-2-kinase/fructose-2,6-bisphosphatase from several tissues a nd species. Expression of PRG1 mRNA was observed in several normal bre ast epithelial and breast cancer cell lines and in a variety of human tissues, with highest expression in the breast, aorta, and brain. In T -47D cells, PRG1 mRNA was rapidly and transiently induced by progestin s, expression peaking between 2 and 4 h and returning to control level s by 12 h. Progestin-induced increases in PRG1 mRNA were inhibited by the progestin antagonist RU 486 and occurred via the progesterone rece ptor. Progestin induction of PRG1 mRNA was also inhibited by actinomyc in D but not by cycloheximide. PRG1 is therefore a novel human gene th at is directly regulated by progestins via the progesterone receptor.