Mullerian Inhibiting Substance (MIS) is a TGF-beta family hormone important in reproductive tract embryogenesis. A temporal correlation has been described between the postmenopausal decrease in MIS and the occurrence of epithelial ovarian cancer. In addition, these tumors demonstrate growth inhibition in vitro after treatment with recombinant human MIS (rhMIS). For these reasons, we have chosen MIS as a potential adjuvant treatment for human ovarian cancer. In this study, a pilot group of patients with stage III/IV ovarian cancer will be screened for MIS binding by flow cytometry, a putative modality for rapid selection of potentially MIS-responsive tumors. Patients who fail to bind MIS will be screened for mutations in the MIS type II receptor gene. This strategy is consistent with a recent report of familial colon cancer patients who have a high incidence of TGF-beta receptor mutations. Binding of MIS or its absence by flow cytometry will be correlated with the presence of wild type or mutant MIS receptor gene and with the presence or absence of growth inhibition in bioassays for functionality. Ultimately, the understanding of these relationships will aid in the design of a clinical trial of MIS as an anti-cancer therapeutic.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA077945-01A1
Application #
2775254
Study Section
Special Emphasis Panel (ZRG2-REB (01))
Program Officer
Lohrey, Nancy
Project Start
1999-08-30
Project End
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Segev, Dorry L; Hoshiya, Yasunori; Hoshiya, Makiko et al. (2002) Mullerian-inhibiting substance regulates NF-kappa B signaling in the prostate in vitro and in vivo. Proc Natl Acad Sci U S A 99:239-44
Segev, D L; Hoshiya, Y; Stephen, A E et al. (2001) Mullerian inhibiting substance regulates NFkappaB signaling and growth of mammary epithelial cells in vivo. J Biol Chem 276:26799-806
Stephen, A E; Masiakos, P T; Segev, D L et al. (2001) Tissue-engineered cells producing complex recombinant proteins inhibit ovarian cancer in vivo. Proc Natl Acad Sci U S A 98:3214-9