Abstract

The hypothesis underlying the work proposed in this application is that a further understanding of MIS downstream signalling will be useful in elucidating the role of this molecule during development, and potentially in new therapeutics for the treatment of tumors that express the MIS receptor. The applicants propose that: """"""""MIS will bind its type II receptor to activate its type I receptor, which in turn will activate a downstream signal cascade, leading to growth arrest and/or death."""""""" The applicants will focus in this project on the MIS specific type 1 receptor. The specific objectives of this application are to: 1) identify the MIS specific type 1 receptor; 2) analyze the role of the MIS type 1 receptor in vivo, using viral vectors, transgenic mice and/or conditional knockout mice; 3) characterize MIS downstream signalling; and 4) identify the target genes regulated by MIS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD032112-08
Application #
6490401
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Taymans, Susan
Project Start
1994-08-01
Project End
2004-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
8
Fiscal Year
2002
Total Cost
$328,698
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Fujino, Akihiro; Arango, Nelson A; Zhan, Yong et al. (2009) Cell migration and activated PI3K/AKT-directed elongation in the developing rat Müllerian duct. Dev Biol 325:351-62
Szotek, Paul P; Chang, Henry L; Zhang, LiHua et al. (2007) Adult mouse myometrial label-retaining cells divide in response to gonadotropin stimulation. Stem Cells 25:1317-25
Gupta, Vandana; Yeo, Giminna; Kawakubo, Hirofumi et al. (2007) Mullerian-inhibiting substance induces Gro-beta expression in breast cancer cells through a nuclear factor-kappaB-dependent and Smad1-dependent mechanism. Cancer Res 67:2747-56
Zhan, Yong; Fujino, Akihiro; MacLaughlin, David T et al. (2006) Mullerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Mullerian duct regression. Development 133:2359-69
Tran, Trinh T; Segev, Dorry L; Gupta, Vandana et al. (2006) Mullerian inhibiting substance regulates androgen-induced gene expression and growth in prostate cancer cells through a nuclear factor-kappaB-dependent Smad-independent mechanism. Mol Endocrinol 20:2382-91
Arango, Nelson A; Huang, Tiffany T; Fujino, Akihiro et al. (2006) Expression analysis and evolutionary conservation of the mouse germ cell-specific D6Mm5e gene. Dev Dyn 235:2613-9
Szotek, Paul P; Pieretti-Vanmarcke, Rafael; Masiakos, Peter T et al. (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A 103:11154-9
Gupta, V; Carey, J L; Kawakubo, H et al. (2005) Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen transgenic mouse mammary carcinoma model. Proc Natl Acad Sci U S A 102:3219-24
Arango, Nelson A; Szotek, Paul P; Manganaro, Thomas F et al. (2005) Conditional deletion of beta-catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium. Dev Biol 288:276-83
Houk, Christopher P; Pearson, Elliot J; Martinelle, Nina et al. (2004) Feedback inhibition of steroidogenic acute regulatory protein expression in vitro and in vivo by androgens. Endocrinology 145:1269-75

Showing the most recent 10 out of 29 publications