DF/HCC Program Affiliation

Gynecologic Cancer

Research Abstract

The focus of my research is to understand the molecular mechanisms used by Müllerian inhibiting substance to exact its effects on the developing reproductive tract and gonads. Müllerian Inhibiting Substance, a member of the TGF-beta superfamily of growth and differentiation factors, is produced by Sertoli cells during embryonal development and is required for normal reproductive development in male embryos. The goals of our efforts are to understand the developmental, cell-specific and sexually dimorphic molecular mechanisms regulating the expression of the MIS type II receptor (MISrII) in Leydig cells, Sertoli cells, and granulosa cells during different stages of development and also in the mesenchymal cells surrounding the Müllerian duct during embryonal development and to uncover target genes whose expression is regulated by MIS signal transduction. These molecular mechanisms can be harnessed for the control of tumors known to respond to MIS, such as Leydig cell or ovarian cancer.

Publications

• Arango NA, Szotek PP, Manganaro TF, Oliva E, Donahoe PK, Teixeira J.Conditional deletion of beta-catenin in the mesenchyme of the developing mouse uterus results in a switch to adipogenesis in the myometrium.Dev Biol 2005 Oct 26.
  16256976
• Arango NA, Pearson EJ, Donahoe PK, Teixeira J.Genomic structure and expression analysis of the mouse testis-specific ribbon protein (Trib) gene.Gene 2004 Dec 8;343(1):221-7.
  15563848
• Trbovich AM, Martinelle N, O'Neill FH, Pearson EJ, Donahoe PK, Sluss PM, Teixeira J.Steroidogenic activities in MA-10 Leydig cells are differentially altered by cAMP and Müllerian inhibiting substance.J Steroid Biochem Mol Biol 2004 Oct;92(3):199-208.
  15555913
• Fynn-Thompson E, Cheng H, Teixeira J.Inhibition of steroidogenesis in Leydig cells by Müllerian-inhibiting substance.Mol Cell Endocrinol 2003 Dec 15;211(1-2):99-104.
  14656482
• Houk CP, Pearson EJ, Martinelle N, Donahoe PK, Teixeira J.Feedback inhibition of steroidogenic acute regulatory protein expression in vitro and in vivo by androgens.Endocrinology 2004 Mar;145(3):1269-75.
  14630719
• Bédécarrats GY, O'Neill FH, Norwitz ER, Kaiser UB, Teixeira J.Regulation of gonadotropin gene expression by Mullerian inhibiting substance.Proc Natl Acad Sci U S A 2003 Aug 5;100(16):9348-53.
  12878721
• Teixeira J, Maheswaran S, Donahoe PK.Müllerian inhibiting substance: an instructive developmental hormone with diagnostic and possible therapeutic applications.Endocr Rev 2001 Oct;22(5):657-74.
  11588147