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Full-Text Articles in Life Sciences
Mmtv-Wnt1 And -Dn89b-Catenin Induce Canonical Signaling In Distinct Progenitors And Differentially Activate Hedgehog Signaling Within Mammary Tumors, Brigitte Teissedre, Alicia Pinderhughes, Angela Incassati, Sarah J. Hatsell, Minoti Hiremath, Pamela Cowin
Mmtv-Wnt1 And -Dn89b-Catenin Induce Canonical Signaling In Distinct Progenitors And Differentially Activate Hedgehog Signaling Within Mammary Tumors, Brigitte Teissedre, Alicia Pinderhughes, Angela Incassati, Sarah J. Hatsell, Minoti Hiremath, Pamela Cowin
Minoti Hiremath
Canonical Wnt/b-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTVWnt1 and MMTV-DN89b-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DN89b-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DN89b-catenin activate canonical Wnt signaling within distinct cell-types. DN89b-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18+ER2PR2CD24highCD49flow profile and progenitor properties. In contrast, …
The Pattern Of Β-Catenin-Responsiveness Within The Mammary Gland Is Regulated By Progesterone Receptor, Minoti Hiremath, John Lydon, Pamela Cowin
The Pattern Of Β-Catenin-Responsiveness Within The Mammary Gland Is Regulated By Progesterone Receptor, Minoti Hiremath, John Lydon, Pamela Cowin
Minoti Hiremath
Experiments involving β-catenin loss- and gain-of-function in the mammary gland have decisively demonstrated the role of this protein in normal alveologenesis. However, the relationship between hormonal and β-catenin signaling has not been investigated. In this study, we demonstrate that activated β-catenin rescues alveologenesis in progesterone receptor (PR; Pgr)-null mice during pregnancy. Two distinct subsets of mammary cells respond to expression of ΔN89β-catenin. Cells at ductal tips are inherently β-catenin-responsive and form alveoli in the absence of PR. However, PR activity confers β-catenin responsiveness to progenitor cells along the lateral ductal borders in the virgin gland. Once activated …