ArticleDevelopmental biology2008
Disruption of the PACAP gene promotes medulloblastoma in ptc1 mutant mice.
Article in Developmental biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Gene Expression Data Mining Reveals the Involvement of GPR55 and Its Endogenous Ligands in Immune Response, Cancer, and Differentiation.International journal of molecular sciences · 2021Article
- Neuronal-driven glioma growth requires Gαi1 and Gαi3.Theranostics · 2021Article
- Pituitary Adenylate Cyclase-Activating Polypeptide: 30 Years in Research Spotlight and 600 Million Years in Service.Journal of clinical medicine · 2019Review
- Differential Expression of Mitochondrial Biogenesis Markers in Mouse and Human SHH-Subtype Medulloblastoma.Cells · 2019Article
- Article
- The G protein Gαs acts as a tumor suppressor in sonic hedgehog signaling-driven tumorigenesis.Cell cycle (Georgetown, Tex.) · 2016Review
- Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer.Current opinion in endocrinology, diabetes, and obesity · 2016Review
- Sonic hedgehog patterning during cerebellar development.Cellular and molecular life sciences : CMLS · 2016Review
- Targeting brain tumor cAMP: the case for sex-specific therapeutics.Frontiers in pharmacology · 2015Article
- Pleiotropic functions of pituitary adenylyl cyclase-activating polypeptide on retinal ontogenesis: involvement of KLF4 in the control of progenitor cell proliferation.Journal of molecular neuroscience : MN · 2014Article
- G-protein-coupled receptors, Hedgehog signaling and primary cilia.Seminars in cell & developmental biology · 2014Review
- Targeted treatment for sonic hedgehog-dependent medulloblastoma.Neuro-oncology · 2014Review
- Target identification for a Hedgehog pathway inhibitor reveals the receptor GPR39.Nature chemical biology · 2014Article
- Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA.Cellular signalling · 2013Article
- Perigestational dietary folic acid deficiency protects against medulloblastoma formation in a mouse model of nevoid basal cell carcinoma syndrome.Nutrition and cancer · 2013Article
- Signaling through the neuropeptide GPCR PAC₁ induces neuritogenesis via a single linear cAMP- and ERK-dependent pathway using a novel cAMP sensor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Distinct patterns of human medulloblastoma dissemination in the developing chick embryo nervous system.Clinical & experimental metastasis · 2012Article
- Pituitary adenylyl cyclase-activating peptide counteracts hedgehog-dependent motor neuron production in mouse embryonic stem cell cultures.Journal of neuroscience research · 2011Article
- Treating brain tumors with PDE4 inhibitors.Trends in pharmacological sciences · 2011Article
- Expression analysis of PAC1-R and PACAP genes in zebrafish embryos.Journal of molecular neuroscience : MN · 2011Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Hedgehog (Hh) proteins and cAMP-dependent protein kinase A (PKA) generally play opposing roles in developmental patterning events. Humans and mice heterozygous for mutations in the sonic hedgehog (Shh) receptor gene patched-1 (ptc1) have an increased incidence of certain types of cancer, including medulloblastoma (MB), a highly aggressive tumor of the cerebellum. Despite the importance of PKA in Hh signaling, little is known about how PKA activity is regulated in the context of Hh signaling, or the consequences of improper regulation. One molecule that can influence PKA activity is pituitary adenylyl cyclase-activating peptide (PACAP), which has been shown to regulate cerebellar granule precursor proliferation in vitro, a cell population thought to give rise to MB. To test for a PACAP/Hh interaction in the initiation or propagation of these tumors, we introduced a PACAP mutation into ptc1 mutant mice. Deletion of a single copy of PACAP increased MB incidence approximate 2.5-fold, to 66%, thereby demonstrating that PACAP exerts a powerful inhibitory action on the induction, growth or survival of these tumors. Tumors from PACAP/ptc1 mutant mice retained PACAP receptor gene expression, and exhibited superinduction of Hh target genes compared to those from ptc1+/- mice. Moreover, PACAP inhibited proliferation of cell lines derived from tumors in a PKA-dependent manner, and inhibited expression of the Hh target gene gli1. The results provide genetic evidence that PACAP acts as a physiological factor that regulates the pathogenesis of Hh pathway-associated MB tumors.
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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.