description): Mucin-type glycoproteins are a major class of apically-secreted/released glycoconjugates of uterine epithelium (UE) of various species, including humans. A series of studies indicates that mucins function as barrier or anti-adhesive molecules. Muc-1 is one of these mucins and is strongly regulated by ovarian steroids in a hormone receptor-dependent fashion. Furthermore, Muc-1 appears to be lost from surface UE during the receptive phase. Recent studies from the investigator's lab indicate that enzymatic removal or genetic ablation of mucin expression converts non-receptive UE to a functionally receptive state in vitro. These observations, along with the observed pattern of mucin expression, are consistent with a role as antiadhesive molecules. Thus, the hypothesis emerges that Muc-1 or mucin removal from surface UE must occur prior to blastocyst attachment. This hypothesis predicts that loss of mucin expression in surface UE serves as a marker of the transition to a receptive uterine state. The investigators will continue their studies of UE mucin expression by studying: 1) steroid hormone regulation of the murine Muc-1 gene; 2) the expression of Muc-1 in human surface UE and UE cell lines and; 3) the function of Muc-1 and other mucins as regulators of embryo attachment in vivo in mice.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD029963-08
Application #
2879375
Study Section
Special Emphasis Panel (SRC (18))
Program Officer
Tasca, Richard J
Project Start
1992-12-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Delaware
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Dharmaraj, N; Chapela, P J; Morgado, M et al. (2014) Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis. Hum Reprod 29:1730-8
Neeraja Dharmaraj; Engel, Brian J; Carson, Daniel D (2013) Activated EGFR stimulates MUC1 expression in human uterine and pancreatic cancer cell lines. J Cell Biochem 114:2314-22
Constantinou, Pamela E; Danysh, Brian P; Dharmaraj, Neeraja et al. (2011) Transmembrane mucins as novel therapeutic targets. Expert Rev Endocrinol Metab 6:835-848
Dharmaraj, Neeraja; Wang, Peng; Carson, Daniel D (2010) Cytokine and progesterone receptor interplay in the regulation of MUC1 gene expression. Mol Endocrinol 24:2253-66
Wang, Peng; Dharmaraj, Neeraja; Brayman, Melissa J et al. (2010) Peroxisome proliferator-activated receptor gamma activation inhibits progesterone-stimulated human MUC1 expression. Mol Endocrinol 24:1368-79
Julian, Joanne; Dharmaraj, Neeraja; Carson, Daniel D (2009) MUC1 is a substrate for gamma-secretase. J Cell Biochem 108:802-15
Dharmaraj, Neeraja; Gendler, Sandra J; Carson, Daniel D (2009) Expression of human MUC1 during early pregnancy in the human MUC1 transgenic mouse model. Biol Reprod 81:1182-8
Al-Shami, Rania; Sorensen, Esben S; Ek-Rylander, Barbro et al. (2005) Phosphorylated osteopontin promotes migration of human choriocarcinoma cells via a p70 S6 kinase-dependent pathway. J Cell Biochem 94:1218-33
Julian, JoAnne; Enders, Allen C; Fazleabas, Asgerally T et al. (2005) Compartmental distinctions in uterine Muc-1 expression during early pregnancy in cynomolgous macaque (Macaca fascicularis) and baboon (Papio anubis). Hum Reprod 20:1493-503
Brayman, Melissa; Thathiah, Amantha; Carson, Daniel D (2004) MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol 2:4

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