Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells.

ABSTRACT: The epithelial components of the mammary gland are thought to arise from stem cells with a capacity for self-renewal and multilineage differentiation. Furthermore, these cells and/or their immediate progeny may be targets for transformation. We have used both in vitro cultivation and a xenograft mouse model to examine the role of hedgehog signaling and Bmi-1 in regulating self-renewal of normal and malignant human mammary stem cells. We show that hedgehog signaling components PTCH1, Gli1, and Gli2 are highly expressed in normal human mammary stem/progenitor cells cultured as mammospheres and that these genes are down-regulated when cells are induced to differentiate. Activation of hedgehog signaling increases mammosphere-initiating cell number and mammosphere size, whereas inhibition of th

SUBMITTER: Liu S 

PROVIDER: S-EPMC4386278 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature