These data indicate that FAE can shift MEC subpopulations, increasing the proportion of cells that are potentially vulnerable to transformation and affecting cancer risk.Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Flow cytometry analysis indicated that FAE females developed tumors with an increased basal cell population. Tumor latency was decreased in the FAE group. Tertiary mammosphere-forming efficiency was greater in the WT glands of FAE animals at 10 weeks of age. In Tg glands, FAE increased the luminal progenitor cell population at 5 weeks of age but did not alter MEC composition at 10 weeks of age. qRT-PCR analysis of total MECs found that Hey1 mRNA expression was increased in the WT FAE group at 10 weeks of age. WT glands of FAE animals exhibited a decreased basal cell population and increased luminal: basal ratio at 10 weeks of age.
A subset of Tg offspring was followed for tumor formation. Thoracic and inguinal mammary glands from wild-type (WT) and transgenic (Tg) female offspring were harvested at 5 and 10 weeks of age and dissociated to yield a single cell suspension enriched for MECs for flow cytometry, mammosphere assay, and gene analysis. Pregnant Friend Virus B NIH Jackson dams bred to MMTV-Wnt1 male mice were given ad libitum access to 5% alcohol in 0.2% saccharin solution from GD9-10 and 10% alcohol in 0.2% saccharin from GD11-GD19 or 0.2% saccharin solution from GD9-GD19. This study tested the hypothesis that FAE shifts the mammary epithelial cell (MEC) composition toward one that promotes tumorigenesis. Fetal alcohol exposure (FAE) increases the risk of mammary tumorigenesis in adult offspring however, the underlying mechanism remains unknown.
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