ArticleBMC medical genomics2008
Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells.
Article in BMC medical genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
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- Ovarian Cancer: A Landscape of Mitochondria with Emphasis on Mitochondrial Dynamics.International journal of molecular sciences · 2023Review
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
- Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer.Journal of ovarian research · 2022Article
- Measuring Spatiotemporal cAMP Dynamics Within an Endogenous Signaling Compartment Using FluoSTEP-ICUE.Methods in molecular biology (Clifton, N.J.) · 2022Article
- AKAP2 is upregulated in ovarian cancer, and promotes growth and migration of cancer cells.Molecular medicine reports · 2017Article
- 8-Cl-cAMP and PKA I-selective cAMP analogs effectively inhibit undifferentiated thyroid cancer cell growth.Endocrine · 2017Article
- miR-200c dampens cancer cell migration via regulation of protein kinase A subunits.Oncotarget · 2015Article
- Implementing fluorescence anisotropy screening and crystallographic analysis to define PKA isoform-selective activation by cAMP analogs.ACS chemical biology · 2013Article
- Article
- 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
- PEA-15 unphosphorylated at both serine 104 and serine 116 inhibits ovarian cancer cell tumorigenicity and progression through blocking β-catenin.Oncogenesis · 2012Article
- Protein kinase A regulates caspase-1 via Ets-1 in bone stromal cell-derived lesions: a link between cyclic AMP and pro-inflammatory pathways in osteoblast progenitors.Human molecular genetics · 2011Article
- Protein kinase A activity and anchoring are required for ovarian cancer cell migration and invasion.PloS one · 2011Article
- Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/- or Rb1+/- backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling.Human molecular genetics · 2010Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIalpha and RIIbeta were stably transfected into cells of the ovarian cancer cell line (OVCAR8).
resultsRIalpha transfected cells exhibit hyper-proliferative growth and RIIbeta transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIalpha, RIIbeta, and parental OVCAR cells. Genes specifically up-regulated in RIalpha cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIbeta cells were enriched for pathways involved in differentiation. A large group of genes (~3600) was regulated along an axis of proliferation/differentiation between RIalpha, parental, and RIIbeta cells. RIalpha/wt and RIIbeta/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation.
conclusionOverexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression.
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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.