ArticleDevelopmental biology2011
Altered differentiation and paracrine stimulation of mammary epithelial cell proliferation by conditionally activated Smoothened.
Article in Developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Advances in Immunocompetent Mouse and Rat Models.Cold Spring Harbor perspectives in medicine · 2024Review
- The Role of Smoothened in Cancer.International journal of molecular sciences · 2020Review
- Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments.International journal of molecular sciences · 2020Review
- Review
- Breast cancer stem cells and the challenges of eradication: a review of novel therapies.Stem cell investigation · 2018Review
- EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- New paradigms for the Hedgehog signaling network in mammary gland development and breast Cancer.Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty.Scientific reports · 2017Article
- Non-autonomous cell proliferation in the mammary gland and cancer.Current opinion in cell biology · 2017Review
- Epithelial and non-epithelialDevelopment (Cambridge, England) · 2017Article
- Blockade of the Hedgehog pathway downregulates estrogen receptor alpha signaling in breast cancer cells.Oncotarget · 2016Article
- The hedgehog pathway in triple-negative breast cancer.Cancer medicine · 2016Review
- A Convenient Method for Evaluating Epithelial Cell Proliferation in the Whole Mammary Glands of Female Mice.Endocrinology · 2016Article
- Developmental Insights into Breast Cancer Intratumoral Heterogeneity.Trends in cancer · 2015Article
- Promising molecular mechanisms responsible for gemcitabine resistance in cancer.Genes & diseases · 2015Review
- An Nfic-hedgehog signaling cascade regulates tooth root development.Development (Cambridge, England) · 2015Article
- Identifying and targeting tumor-initiating cells in the treatment of breast cancer.Endocrine-related cancer · 2015Review
- The Hedgehog pathway: role in cell differentiation, polarity and proliferation.Archives of toxicology · 2015Review
- Paracrine signaling in mammary gland development: what can we learn about intratumoral heterogeneity?Breast cancer research : BCR · 2014Review
- Targeting hedgehog signaling in cancer: research and clinical developments.OncoTargets and therapy · 2013Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The Hedgehog (Hh) signaling network is critical for patterning and organogenesis in mammals, and has been implicated in a variety of cancers. Smoothened (Smo), the gene encoding the principal signal transducer, is overexpressed frequently in breast cancer, and constitutive activation in MMTV-SmoM2 transgenic mice caused alterations in mammary gland morphology, increased proliferation, and changes in stem/progenitor cell number. Both in transgenic mice and in clinical specimens, proliferative cells did not usually express detectable Smo, suggesting the hypothesis that Smo functioned in a non-cell autonomous manner to stimulate proliferation. Here, we employed a genetically tagged mouse model carrying a Cre-recombinase-dependent conditional allele of constitutively active Smo (SmoM2) to test this hypothesis. MMTV-Cre- or adenoviral-Cre-mediated SmoM2 expression in the luminal epithelium, but not in the myoepithelium, was required for the hyper-proliferative phenotypes. High levels of proliferation were observed in cells adjacent or in close-proximity to Smo expressing cells demonstrating that SmoM2 expressing cells were stimulating proliferation via a paracrine or juxtacrine mechanism. In contrast, Smo expression altered luminal cell differentiation in a cell-autonomous manner. SmoM2 expressing cells, purified by fluorescence activated cell sorting (FACS) via the genetic fluorescent tag, expressed high levels of Ptch2, Gli1, Gli2, Jag2 and Dll-1, and lower levels of Notch4 and Hes6, in comparison to wildtype cells. These studies provide insight into the mechanism of Smo activation in the mammary gland and its possible roles in breast tumorigenesis. In addition, these results also have potential implications for the interpretation of proliferative phenotypes commonly observed in other organs as a consequence of hedgehog signaling activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.