| A high priority in basic research of the mammary gland is to identify novel morphogens and growth stimulatory molecules that contribute to the development of mammary cancer. One such candidate molecule is called epimorphin/syntaxin-2 (EPM). EPM was first identified as a stromal morphogen that could stimulate the differentiation of dermal and lung epithelium. Subsequently, EPM was found to be expressed in the mammary gland and was shown to stimulate distinct modes of mammary epithelial morphogenesis in culture. Transgenic mice overexpressing EPM in the mouse mammary gland were found to show enlarged mammary ducts (ectasia) during pregnancy.; Here a combination of mouse models and cell culture models are utilized to investigate the possible role of EPM in the development of the mammary gland and in mammary gland cancer. We report that EPM levels are highly expressed during peak times of morphogenesis in the mammary gland, suggesting a connection between EPM and development of the mammary gland. In addition, we found that EPM is under negative regulation by 17beta-estradiol and progesterone, endocrine hormones known to stimulate mammary gland development. We asked the question whether deregulated EPM leads to aberrant mammary gland development. We found that when EPM is overexpressed in a transgenic mouse model precocious ductal and alveolar development occur, enlarged mammary ducts form, mammary gland involution is delayed, and mice are susceptible to cancer later in life. |
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