ArticleOncogene2000
PI-3-kinase is an essential anti-apoptotic effector in the proliferative response of primary human epithelial cells to mutant RAS.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 68 citations in OpenAlex.
- Review
- Combination of KRAS gene silencing and PI3K inhibition for ovarian cancer treatment.Journal of controlled release : official journal of the Controlled Release Society · 2020Article
- Persistent ERK/MAPK activation promotes lactotrope differentiation and diminishes tumorigenic phenotype.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2.Carcinogenesis · 2013Article
- RAS Interaction with PI3K: More Than Just Another Effector Pathway.Genes & cancer · 2011Article
- Mutational and immunohistochemical study of the PI3K/Akt pathway in papillary thyroid carcinoma in Greece.Endocrine pathology · 2010Article
- Increased STAT-3 and synchronous activation of Raf-1-MEK-1-MAPK, and phosphatidylinositol 3-Kinase-Akt-mTOR pathways in atypical and anaplastic meningiomas.Journal of neuro-oncology · 2009Article
- Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia.Leukemia · 2008Review
- The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.Current genomics · 2007Article
- Targeting the RAF/MEK/ERK, PI3K/AKT and p53 pathways in hematopoietic drug resistance.Advances in enzyme regulation · 2007Article
- Mutant ras-induced proliferation of human thyroid epithelial cells requires three effector pathways.Oncogene · 2004Article
- Chromosomal imbalances associated with anaplastic transformation of follicular thyroid carcinomas.British journal of cancer · 2004Article
- The dark side of Ras: regulation of apoptosis.Oncogene · 2003Review
- Review
- Isoprenylcysteine carboxyl methyltransferase activity modulates endothelial cell apoptosis.Molecular biology of the cell · 2003Article
- Article
- Differential mechanisms of constitutive Akt/PKB activation and its influence on gene expression in pancreatic cancer cells.Japanese journal of cancer research : Gann · 2002Article
- Article
- Article
- A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In contrast to its growth-inhibitory effect on primary mesenchymal cells, RAS oncogene activation induces a proliferative phenotype in normal human thyroid epithelial cells in vitro, consistent with its putative role in tumour initiation. Using this model, we previously showed that activation of the MAP kinase (MAPK) pathway is necessary, but not sufficient for the proliferative response to mutant (V12) H-RAS. Here we extend this work to show that another major RAS effector-- phosphatidylinositol-3-kinase (PI-3-K)--while also insufficient alone, is able to synergize with MAPK activation to mimic the effect of mutant RAS, albeit at reduced efficiency. Furthermore we show that PI-3-K is an absolute requirement for the proliferative response to RAS in these cells, acting via suppression of RAS-induced apoptosis. These data extend our understanding of RAS signalling in a clinically-relevant cell context and point to the use of PI-3-K inhibitors as potential therapeutic agents for targetting human cancers induced by RAS mutation.
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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.