ArticleMolecular and cellular biology1996
Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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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Who cites it
29 citing papers in PubMed, 112 citations in OpenAlex.
- Lentivirus‑delivered nemo‑like kinase small interfering RNA inhibits laryngeal cancer cell proliferation in vitro.Molecular medicine reports · 2015Article
- N-Polybenzylated alicyclic 1,2-diamines: cytotoxicity and G1 phase arrest in cancer cell line.Molecular diversity · 2014Article
- A rapid microwell fluorescence immunoassay for cellular protein detection.Biological procedures online · 2008Article
- Effects of the environmental mammary carcinogen 6-nitrochrysene on p53 and p21(Cip1) protein expression and cell cycle regulation in MCF-7 and MCF-10A cells.Chemico-biological interactions · 2007Article
- Stabilization of SMAR1 mRNA by PGA2 involves a stem loop structure in the 5' UTR.Nucleic acids research · 2007Article
- PTEN expression in PTEN-null leukaemic T cell lines leads to reduced proliferation via slowed cell cycle progression.Oncogene · 2003Article
- Influence of the RNA-binding protein HuR in pVHL-regulated p53 expression in renal carcinoma cells.Molecular and cellular biology · 2003Article
- Differential expression of cyclin D1 in the human hair follicle.The American journal of pathology · 2003Article
- Inhibition of the proteasome by lactacystin enhances oligodendroglial cell differentiation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003Article
- von Hippel-Lindau protein-mediated repression of tumor necrosis factor alpha translation revealed through use of cDNA arrays.Molecular and cellular biology · 2003Article
- Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells.Leukemia · 2002Article
- Cyclopentenone causes cell cycle arrest and represses cyclin D1 promoter activity in MCF-7 breast cancer cells.Oncogene · 2002Article
- p21(waf) correlates with DNA replication but not with prognosis in invasive breast cancer.Journal of clinical pathology · 2001Article
- Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence.Molecular and cellular biology · 2001Article
- Integration of the pRB and p53 cell cycle control pathways.Journal of neuro-oncology · 2001Review
- Down-regulation of cyclin D1 expression by prostaglandin A(2) is mediated by enhanced cyclin D1 mRNA turnover.Molecular and cellular biology · 2000Article
- Multidrug resistance protein MRP1 protects against the toxicity of the major lipid peroxidation product 4-hydroxynonenal.The Biochemical journal · 2000Article
- Contact with fibrillar collagen inhibits melanoma cell proliferation by up-regulating p27KIP1.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- pRb and Cdk regulation by N-(4-hydroxyphenyl)retinamide.Oncogene · 2000Article
- Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.
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