Mullerian Inhibiting Substance, a product of the fetal testis, is a large molecular weight glycoprotein which initiates regression of the Mullerian duct, the anlagan of the uterus, fallopian tube, and upper vagina. Donahoe and co-workers 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 fold from 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. We propose to use recombinant DNA technology to isolate the genes for bovine and human MIS and to express those genes in E. coli or animal cells. We will then develop a process for purifying large amounts of human MIS in order to test the efficacy of MIS as an anti-cancer drug in a clinical setting. Specifically in Phase I, we propose to sequence peptides of bovine MIS and generate oligonucleotide probes. The probes will be used to isolate the bovine clone from a cDNA library, which will then be used to isolate the human gene.
| Cate, R L; Mattaliano, R J; Hession, C et al. (1986) Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells. Cell 45:685-98 |
| Cate, R L; Ninfa, E G; Pratt, D J et al. (1986) Development of mullerian inhibiting substance as an anti-cancer drug. Cold Spring Harb Symp Quant Biol 51 Pt 1:641-7 |
