ArticleMolecular and cellular biology1999
Cyclin D1 expression mediated by phosphatidylinositol 3-kinase through mTOR-p70(S6K)-independent signaling in growth factor-stimulated NIH 3T3 fibroblasts.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 182 citations in OpenAlex.
- Tetraarsenic Hexoxide Enhanced the Anticancer Effects ofInternational journal of molecular sciences · 2025Article
- F-box protein FBXO32 ubiquitinates and stabilizes D-type cyclins to drive cancer progression.Nature communications · 2025Article
- Molecular Alterations in Gastric Intestinal Metaplasia Shed Light on Alteration of Methionine Metabolism: Insight into New Diagnostic and Treatment Approaches.Biomedicines · 2025Review
- Mitogen signaling strength and duration can control cell cycle decisions.Science advances · 2024Review
- Targeting cyclin D1 as a therapeutic approach for papillary thyroid carcinoma.Frontiers in oncology · 2023Review
- Dual PI3K/Akt Inhibitors Bearing Coumarin-Thiazolidine Pharmacophores as Potential Apoptosis Inducers in MCF-7 Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Stimulation of ROS Generation by Extract ofAntioxidants (Basel, Switzerland) · 2021Article
- Review
- Article
- The present and future of PI3K inhibitors for cancer therapy.Nature cancer · 2021Article
- Primary cells derived from Tuberous Sclerosis Complex patients show autophagy alteration in the haploinsufficiency state.Genetics and molecular biology · 2021Article
- Cyclin D degradation by E3 ligases in cancer progression and treatment.Seminars in cancer biology · 2020Review
- Disruption of AKAP-PKA Interaction Induces Hypercontractility With Concomitant Increase in Proliferation Markers in Human Airway Smooth Muscle.Frontiers in cell and developmental biology · 2020Article
- Dual-Inhibition of mTOR and Bcl-2 Enhances the Anti-tumor Effect of Everolimus against Renal Cell CarcinomaJournal of Cancer · 2019Article
- Synergy of WEE1 and mTOR Inhibition in MutantClinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- HDAC8 Prevents Anthrax Lethal Toxin-induced Cell Cycle Arrest through Silencing PTEN in Human Monocytic THP-1 Cells.Toxins · 2017Article
- Cyclin D1, cancer progression, and opportunities in cancer treatment.Journal of molecular medicine (Berlin, Germany) · 2016Review
- Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Review
- Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions.Discovery medicine · 2016Article
- MicroRNA-199a-3p suppresses glioma cell proliferation by regulating the AKT/mTOR signaling pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphatidylinositol (PI) 3-kinase is required for G1 to S phase cell cycle progression stimulated by a variety of growth factors and is implicated in the activation of several downstream effectors, including p70(S6K). However, the molecular mechanisms by which PI 3-kinase is engaged in activation of the cell cycle machinery are not well understood. Here we report that the expression of a dominant negative (DN) form of either the p110alpha catalytic or the p85 regulatory subunit of heterodimeric PI 3-kinase strongly inhibited epidermal growth factor (EGF)-induced upregulation of cyclin D1 protein in NIH 3T3(M17) fibroblasts. The PI 3-kinase inhibitors LY294002 and wortmannin completely abrogated increases in both mRNA and protein levels of cyclin D1 and phosphorylation of pRb, inducing G1 arrest in EGF-stimulated cells. By contrast, rapamycin, which potently suppressed p70(S6K) activity throughout the G1 phase, had little inhibitory effect, if any, on either of these events. PI 3-kinase, but not rapamycin-sensitive pathways, was also indispensable for upregulation of cyclin D1 mRNA and protein by other mitogens in NIH 3T3 (M17) cells and in wild-type NIH 3T3 cells as well. We also found that an enforced expression of wild-type p110 was sufficient to induce cyclin D1 protein expression in growth factor-deprived NIH 3T3(M17) cells. The p110 induction of cyclin D1 in quiescent cells was strongly inhibited by coexpression of either of the PI 3-kinase DN forms, and by LY294002, but was independent of the Ras-MEK-ERK pathway. Unlike mitogen stimulation, the p110 induction of cyclin D1 was sensitive to rapamycin. These results indicate that the catalytic activity of PI 3-kinase is necessary, and could also be sufficient, for upregulation of cyclin D1, with mTOR signaling being differentially required depending upon cellular conditions.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.