Differential expression of TGF-β isoforms during postlactational mammary gland involution

Abstract.

After cessation of lactation, the mammary gland undergoes involution, which is characterized by a massive epithelial cell death and proteolytic degradation of the extracellular matrix. Whereas the expression patterns and also the function of TGF-β isoforms during mammary gland branching morphogenesis and lactation are well understood, their expression during postlactational involution and therefore a possible role in this process is poorly known. In this study we show that TGF-β3 expression is dramatically induced (>fivefold) during mouse mammary gland involution when compared to that of virgin mouse, reaching a maximal expression level at day 4 after weaning. In contrast, other TGF-β isoforms do not display significant increase in expression during involution (TGF-β1, 1.3-fold and TGF-β2, <1.5-fold) when compared to that of virgin or lactating mice. During mammary gland involution, TGF-β3 is expressed in the epithelial layer and particularly in myoepithelial cells. A comparison of the kinetics of TGF-β3 expression to that of programmed cell death and degradation of the basement membrane suggests that TGF-β3 functions in the remodeling events of the extracellular matrix during the second stage of involution.