Induction of lactoferrin expression in murine ES cells by retinoic acid and estrogen

Lactoferrin is an iron-binding glycoprotein present in high concentrations in milk and exocrine fluids such as bile and tears. Many functions have been attributed to lactoferrin, including antimicrobial and antiviral activities, immunomodulation, and cell growth regulation. Lactoferrin expression is controlled by different regulators, including retinoic acid and estrogen. However, the expression pattern of lactoferrin in mammalian early development has not yet been reported. Murine embryonic stem cells are pluripotent cells that can contribute to all tissues and were used for this study. We show here that while no lactoferrin protein or mRNA was detected in untreated murine embryonic stem cells, retinoic acid and estrogen can induce high levels lactoferrin expression in these cells. Expression, demonstrated by reverse transcription-polymerase chain reaction, Western blot, immunofluorescence, and ELISA assay, was dose and time dependent. Our study provides an in vitro model for examining lactoferrin expression in early development and differentiation.