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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (SRC (18))
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University of Texas MD Anderson Cancer Center
Other Domestic Higher Education
United States
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Julian, Joanne; Dharmaraj, Neeraja; Carson, Daniel D (2009) MUC1 is a substrate for gamma-secretase. J Cell Biochem 108:802-15
Wang, Peng; Julian, Joanne A; Carson, Daniel D (2008) The MUC1 HMFG1 glycoform is a precursor to the 214D4 glycoform in the human uterine epithelial cell line, HES. Biol Reprod 78:290-8
Brayman, Melissa Jo; Dharmaraj, Neeraja; Lagow, Errin et al. (2007) MUC1 expression is repressed by protein inhibitor of activated signal transducer and activator of transcription-y. Mol Endocrinol 21:2725-37
Carson, Daniel D; Julian, JoAnne; Lessey, Bruce A et al. (2006) MUC1 is a scaffold for selectin ligands in the human uterus. Front Biosci 11:2903-8
Brayman, Melissa J; Julian, JoAnne; Mulac-Jericevic, Biserka et al. (2006) Progesterone receptor isoforms A and B differentially regulate MUC1 expression in uterine epithelial cells. Mol Endocrinol 20:2278-91
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
Tang, Meiyi; Mikhailik, Anatoly; Pauli, Ilse et al. (2005) Decidual differentiation of stromal cells promotes Proprotein Convertase 5/6 expression and lefty processing. Endocrinology 146:5313-20
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
Tang, Meiyi; Xu, Yun; Julian, Joanne et al. (2005) Lefty is expressed in mouse endometrium in estrous cycle and peri-implantation period. Hum Reprod 20:872-80
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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