BACKGROUND: Fetal alcohol exposure (FAE) increases the risk of mammary tumorigenesis in adult offspring; however, the underlying mechanism remains unknown. This study tested the hypothesis that FAE shifts the mammary epithelial cell (MEC) composition toward one that promotes tumorigenesis. METHODS: 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. 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. A subset of Tg offspring was followed for tumor formation. RESULTS: WT glands of FAE animals exhibited a decreased basal cell population and increased luminal: basal ratio 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. 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. Tertiary mammosphere-forming efficiency was greater in the WT glands of FAE animals at 10 weeks of age. Tumor latency was decreased in the FAE group. Flow cytometry analysis indicated that FAE females developed tumors with an increased basal cell population. CONCLUSIONS: These data indicate that FAE can shift MEC subpopulations, increasing the proportion of cells that are potentially vulnerable to transformation and affecting cancer risk.
BACKGROUND: Fetal alcohol exposure (FAE) increases the risk of mammary tumorigenesis in adult offspring; however, the underlying mechanism remains unknown. This study tested the hypothesis that FAE shifts the mammary epithelial cell (MEC) composition toward one that promotes tumorigenesis. METHODS: 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. 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. A subset of Tg offspring was followed for tumor formation. RESULTS: WT glands of FAE animals exhibited a decreased basal cell population and increased luminal: basal ratio 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. 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. Tertiary mammosphere-forming efficiency was greater in the WT glands of FAE animals at 10 weeks of age. Tumor latency was decreased in the FAE group. Flow cytometry analysis indicated that FAE females developed tumors with an increased basal cell population. CONCLUSIONS: These data indicate that FAE can shift MEC subpopulations, increasing the proportion of cells that are potentially vulnerable to transformation and affecting cancer risk.
Authors: Tiffany A Polanco; Catina Crismale-Gann; Kenneth R Reuhl; Dipak K Sarkar; Wendie S Cohick Journal: Alcohol Clin Exp Res Date: 2010-11 Impact factor: 3.455
Authors: Elgene Lim; François Vaillant; Di Wu; Natasha C Forrest; Bhupinder Pal; Adam H Hart; Marie-Liesse Asselin-Labat; David E Gyorki; Teresa Ward; Audrey Partanen; Frank Feleppa; Lily I Huschtscha; Heather J Thorne; Stephen B Fox; Max Yan; Juliet D French; Melissa A Brown; Gordon K Smyth; Jane E Visvader; Geoffrey J Lindeman Journal: Nat Med Date: 2009-08-02 Impact factor: 53.440
Authors: Ana M Soto; Laura N Vandenberg; Maricel V Maffini; Carlos Sonnenschein Journal: Basic Clin Pharmacol Toxicol Date: 2008-02 Impact factor: 4.080
Authors: Yixiao Feng; Mia Spezia; Shifeng Huang; Chengfu Yuan; Zongyue Zeng; Linghuan Zhang; Xiaojuan Ji; Wei Liu; Bo Huang; Wenping Luo; Bo Liu; Yan Lei; Scott Du; Akhila Vuppalapati; Hue H Luu; Rex C Haydon; Tong-Chuan He; Guosheng Ren Journal: Genes Dis Date: 2018-05-12