ArticleOncogene2003
Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth factor independence of pancreatic cancer cell lines.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 65 citations in OpenAlex.
- The miR-1305/KLF5 negative regulatory loop affects pancreatic cancer cell proliferation and apoptosis.Human cell · 2025Article
- Resistance to Trastuzumab.Cancers · 2022Review
- The Ups and Downs of STAT Inhibition in Acute Myeloid Leukemia.Biomedicines · 2021Review
- Article
- Doxorubicin and Varlitinib Delivery by Functionalized Gold Nanoparticles Against Human Pancreatic Adenocarcinoma.Pharmaceutics · 2019Article
- Boehmenan, a Lignan From the Chinese Medicinal Plant Clematis armandii, Inhibits A431 Cell Growth via Blocking p70S6/S6 Kinase Pathway.Integrative cancer therapies · 2017Article
- HER2 in Breast Cancer Stemness: A Negative Feedback Loop towards Trastuzumab Resistance.Cancers · 2017Review
- Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer.Science translational medicine · 2015Article
- Inhibiting signal transducer and activator of transcription-3 increases response to gemcitabine and delays progression of pancreatic cancer.Molecular cancer · 2013Article
- Protein kinase C zeta regulates human pancreatic cancer cell transformed growth and invasion through a STAT3-dependent mechanism.PloS one · 2013Article
- Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways.International journal of cancer · 2012Article
- Activation of PDGFr-β Signaling Pathway after Imatinib and Radioimmunotherapy Treatment in Experimental Pancreatic Cancer.Cancers · 2011Article
- A functional nuclear epidermal growth factor receptor, SRC and Stat3 heteromeric complex in pancreatic cancer cells.PloS one · 2011Article
- Identification of a structural motif in the tumor-suppressive protein GRIM-19 required for its antitumor activity.The American journal of pathology · 2010Article
- Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo.European journal of cancer (Oxford, England : 1990) · 2010Article
- Enhanced sensitivity of pancreatic cancer cells to concurrent inhibition of aberrant signal transducer and activator of transcription 3 and epidermal growth factor receptor or Src.The Journal of pharmacology and experimental therapeutics · 2010Article
- Differential roles of cyclin D1 and D3 in pancreatic ductal adenocarcinoma.Molecular cancer · 2010Article
- Insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth.World journal of gastroenterology · 2009Article
- Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts.British journal of cancer · 2009Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) cell lines, MIA PaCa-2, and UK Pan-1, were used to investigate the role of ErbB2 in PDAC oncogenesis. Both these cell lines exhibit exogenous growth factor-independent proliferation that was attributed to the production of autocrine growth factors and/or overexpression of growth factor receptors. The exogenous growth factor-independent phenotype displayed by these PDAC cell lines was dependent on ErbB2 kinase activity since treatment of cells with tyrphostin AG879 prevented serum-free media (SFM) induction of cell proliferation. We determined that ErbB2 kinase contributed to aberrant cell cycle regulation in PDAC through the induction of cyclin D1 levels and the suppression of p21(Cip1) and p27(Kip1). Inhibition of ErbB2 kinase led to cell cycle arrest marked by an increased association of p27(Kip1) with cdk2 and reduced levels of phosphorylated pRb. We further observed constitutive STAT3 activation in the PDAC cell lines and an increase in STAT3 activation upon stimulating quiescent cells with SFM. Inhibitors of ErbB2 kinase blocked STAT3 activation, whereas inhibition of EGFR kinase led to a slight reduction of STAT3 activation. STAT3 was coimmunoprecipitated with ErbB2. SFM stimulation caused an increase in the association of ErbB2 and STAT3, which was blocked by inhibition of ErbB2 kinase. Expression of a STAT3 dominant negative prevented SFM-stimulated cell proliferation of MIA PaCa-2 cells, suggesting that activation of STAT3 by ErbB2 is required for a growth factor-independent phenotype of these cells. Consistent with this observation in PDAC cell lines, we found that most PDAC tumor specimens (10 of 11) showed constitutive activation of STAT3 and that ErbB2 was readily detected in most of these tumors (nine of 11). We believe that these findings indicate a novel mechanism of oncogenesis in PDAC and may suggest future therapeutic strategies in the treatment of PDAC.
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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.