MYOEPITHELIAL CELL-DIFFERENTIATION IN THE DEVELOPING MAMMARY-GLAND - PROGRESSIVE ACQUISITION OF SMOOTH-MUSCLE PHENOTYPE

The most important portion of the mammary gland development occurs pos tnatally, with distinct periods of intensive morphogenesis taking plac e between birth and puberty and during pregnancy and lactation. To cha racterize the differentiation process of mammary myoepithelial cells, we have studied the expression patterns of several smooth muscle pheno typic markers, including contractile proteins, alpha-smooth muscle-act in (alpha-SM-actin), smooth muscle myosin heavy chains (SM-MHC), and c alponin; components of cell-extracellular matrix adherens junctions, p hosphoglucomutase-related protein (PGM), vinculin variants, integrin s ubunits; and laminin variant chains in the developing rat mammary glan d using immunofluorescence microscopy. alpha-SM-actin- and SM-MHC-posi tive cells were found first in newborn animals, while calponin, PGM an d alpha(1) integrin subunit began to be expressed in prepubertal anima ls (1.5 weeks). Vinculin, beta(1) and alpha(3) integrin subunits were largely confined to the basal cell layer at all developmental stages e xamined with greater staining starting at 1.5 weeks. Meta-vinculin was identified only in myoepithelial cells of the lactating gland. gamma 1 laminin chain was present in the mammary gland basement membrane thr oughout development, while the beta 2 chain was revealed in 3-week-old animals and accumulated later in postpubertal animals (7 weeks). Simi larly, beta 2 laminin chain was absent from the forming alveoli baseme nt membrane in pregnant rats and started to accumulate in the lactatin g gland. In addition to temporal changes, we have observed spatial dif ferences in the distribution of the phenotypic markers. Both in pre- a nd in postpubertal animals, alpha-SM-actin- and SM-MHC-positive cells of the growing ductal ends contained low amounts if any of calponin, P GM, and beta 2 laminin chain. We conclude that during postnatal develo pment, mammary myoepithelial cells progressively acquire a differentia ted phenotype as revealed by the expression of various smooth muscle m arkers. Maturation of the myoepithelial cells is accompanied by upregu lation of the smooth muscle integrin expression followed by accumulati on of beta 2-containing laminin variant. Thus, changes in adhesion sys tem parallel with the myoepithelial cell differentiation. (C) 1995 Wil ey-Liss, Inc.