ArticleDevelopmental biology2011
PI3K/mTOR signaling regulates prostatic branching morphogenesis.
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 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- hsa_circ_0000417 downregulation suppresses androgen receptor expression and apoptotic signals in human foreskin fibroblasts via sponging miR-6756-5p.Molecular biology reports · 2023Article
- Neuronal-epithelial cross-talk drives acinar specification via NRG1-ERBB3-mTORC2 signaling.Developmental cell · 2022Article
- Lifetime Impact of Cow's Milk on Overactivation of mTORC1: From Fetal to Childhood Overgrowth, Acne, Diabetes, Cancers, and Neurodegeneration.Biomolecules · 2021Review
- Organotypic culture assays for murine and human primary and metastatic-site tumors.Nature protocols · 2020Article
- Pluripotent stem cell differentiation as an emerging model to study human prostate development.Stem cell research & therapy · 2020Review
- Prostate Organogenesis.Cold Spring Harbor perspectives in medicine · 2018Review
- RET-mediated glial cell line-derived neurotrophic factor signaling inhibits mouse prostate development.Development (Cambridge, England) · 2017Article
- Prostate organogenesis: tissue induction, hormonal regulation and cell type specification.Development (Cambridge, England) · 2017Review
- Patterned cell and matrix dynamics in branching morphogenesis.The Journal of cell biology · 2017Review
- Milk--A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation.International journal of molecular sciences · 2015Review
- Glial cell line-derived neurotrophic factor induces cell proliferation in the mouse urogenital sinus.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Article
- Three-dimensional organotypic culture: experimental models of mammalian biology and disease.Nature reviews. Molecular cell biology · 2014Review
- Notch signaling in prostate cancer: a moving target.The Prostate · 2014Review
- mTOR signaling feedback modulates mammary epithelial differentiation and restrains invasion downstream of PTEN loss.Cancer research · 2013Article
- Article
- Evidence for a pro-proliferative feedback loop in prostate cancer: the role of Epac1 and COX-2-dependent pathways.PloS one · 2013Article
- Wnt signaling though beta-catenin is required for prostate lineage specification.Developmental biology · 2012Article
- Visualization and quantification of mouse prostate development by in situ hybridization.Differentiation; research in biological diversity · 2012Article
- The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer.Nutrition & metabolism · 2012Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Prostatic branching morphogenesis is an intricate event requiring precise temporal and spatial integration of numerous hormonal and growth factor-regulated inputs, yet relatively little is known about the downstream signaling pathways that orchestrate this process. In this study, we use a novel mesenchyme-free embryonic prostate culture system, newly available mTOR inhibitors and a conditional PTEN loss-of-function model to investigate the role of the interconnected PI3K and mTOR signaling pathways in prostatic organogenesis. We demonstrate that PI3K levels and PI3K/mTOR activity are robustly induced by androgen during murine prostatic development and that PI3K/mTOR signaling is necessary for prostatic epithelial bud invasion of surrounding mesenchyme. To elucidate the cellular mechanism by which PI3K/mTOR signaling regulates prostatic branching, we show that PI3K/mTOR inhibition does not significantly alter epithelial proliferation or apoptosis, but rather decreases the efficiency and speed with which the developing prostatic epithelial cells migrate. Using mTOR kinase inhibitors to tease out the independent effects of mTOR signaling downstream of PI3K, we find that simultaneous inhibition of mTORC1 and mTORC2 activity attenuates prostatic branching and is sufficient to phenocopy combined PI3K/mTOR inhibition. Surprisingly, however, mTORC1 inhibition alone has the reverse effect, increasing the number and length of prostatic branches. Finally, simultaneous activation of PI3K and downstream mTORC1/C2 via epithelial PTEN loss-of-function also results in decreased budding reversible by mTORC1 inhibition, suggesting that the effect of mTORC1 on branching is not primarily mediated by negative feedback on PI3K/mTORC2 signaling. Taken together, our data point to an important role for PI3K/mTOR signaling in prostatic epithelial invasion and migration and implicates the balance of PI3K and downstream mTORC1/C2 activity as a critical regulator of prostatic epithelial morphogenesis.
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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.