MULLERIAN INHIBITING SUBSTANCE

MULLERIAN INHIBITING SUBSTANCE (MIS), A PRODUCT OF THE FETALTESTIS, IA A HIGH MOLECULAR WEIGHT GLYCOPROTEIN THAT INITIATES REGRESSION OF THE MULLERIAN DUCT, THE ANLAGEN OF THE UTERUS, FALLOPIAN TUBE, AND UPPER VAGINA. BIOGEN RESEARCHERS HAVE SHOWN THAT THIS FETAL REGRESSOR CAN ALSO INHIBIT THE GROWTH OF SOME TUMORS DERIVED FROM THE CELL TYPES WHICH RESPOND TO THE FETAL REGRESSOR IN EMBRYONIC LIFE. BIOLOGICALLY ACTIVE MIS HAS BEEN PURIFIED 30,000-FOLDFROM BOVINE TESTIS. HOWEVER, THE AMOUNT OF BOVINE MIS THAT CAN BE ISOLATED BY CONVENTIONAL MEANS IS TOO LOW TO PERMIT BROAD ONCOLOGICAL STUDIES, AND THE HUMAN PROTEIN IS NOT AVAILABLE. BIOGEN PROPOSES TO USE RECOMBINANT DNA TECHNOLOGY TO ISOLATE THE GENES FOR BOVINE AND HUMAN MIS ANDTO EXPRESS THOSE GENES IN E. COLI OR ANIMAL CELLS. A PROCESS FOR PURIFYING LARGE AMOUNTS OF HUMAN MIS IN ORDER TOTEST THE EFFICACY OF MIS AS AN ANTICANCER DRUG IN A CLINICALSETTING WILL THEN BE DEVELOPED. SPECIFICALLY IN PHASE I, PEPTIDES OF BOVINE MIS AND GENERATE OLIGONUCLEOTIDE PROBES WILL BE SEQUENCED. THE PROBES WILL BE USED TO ISOLATE THE BOVINE CLONE FROM A CDNA LIBRARY, WHICH WILL THEN BE USED TOISOLATE THE HUMAN GENE.