ArticleJournal of experimental & clinical cancer research : CR2010
PKCalpha-induced drug resistance in pancreatic cancer cells is associated with transforming growth factor-beta1.
Article in Journal of experimental & clinical cancer research : CR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment.Nature genetics · 2024Article
- Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines.International journal of molecular sciences · 2023Article
- Review
- Identification of Novel Anthracycline Resistance Genes and Their Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2021Article
- AANG: A natural compound formula for overcoming multidrug resistance via synergistic rebalancing the TGF-β/Smad signalling in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2021Article
- Article
- TGF-β Signaling and Resistance to Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- A Feedback Loop between Hypoxia and Matrix Stress Relaxation Increases Oxygen-Axis Migration and Metastasis in Sarcoma.Cancer research · 2019Article
- Protein kinase Cα-mediated phosphorylation of Twist1 at Ser-144 prevents Twist1 ubiquitination and stabilizes it.The Journal of biological chemistry · 2019Article
- Protein kinase C isoforms in the normal pancreas and in pancreatic disease.Cellular signalling · 2017Review
- Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance.Scientific reports · 2016Article
- Protein kinase Cα mediates erlotinib resistance in lung cancer cells.Molecular pharmacology · 2015Article
- Targeting protein kinase C subtypes in pancreatic cancer.Expert review of anticancer therapy · 2015Review
- Mining for Candidate Genes Related to Pancreatic Cancer Using Protein-Protein Interactions and a Shortest Path Approach.BioMed research international · 2015Article
- TGFβ induces "BRCAness" and sensitivity to PARP inhibition in breast cancer by regulating DNA-repair genes.Molecular cancer research : MCR · 2014Article
- Targeting tight junctions during epithelial to mesenchymal transition in human pancreatic cancer.World journal of gastroenterology · 2014Review
- Ellagic acid checks lymphoma promotion via regulation of PKC signaling pathway.Molecular biology reports · 2013Article
- The kinase PKCα selectively upregulates interleukin-17A during Th17 cell immune responses.Immunity · 2013Article
- Molecular predictors of gemcitabine response in pancreatic cancer.World journal of gastrointestinal oncology · 2011Article
- Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling.Journal of proteome research · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrug resistance remains a great challenge in the treatment of pancreatic cancer. The goal of this study was to determine whether TGF-beta1 is associated with drug resistance in pancreatic cancer.
methodsPancreatic cancer BxPC3 cells were stably transfected with TGF-beta1 cDNA. Cellular morphology and cell cycle were determined and the suppressive subtracted hybridization (SSH) assay was performed to identify differentially expressed genes induced by TGF-beta1. Western blotting and immunohistochemistry were used to detect expression of TGF-beta1-related genes in the cells and tissue samples. After that, the cells were further treated with an anti-cancer drug (e.g., cisplatin) after pre-incubated with the recombinant TGF-beta1 plus PKCalpha inhibitor Gö6976. TGF-beta1 type II receptor, TbetaRII was also knocked down using TbetaRII siRNA to assess the effects of these drugs in the cells. Cell viability was assessed by MTT assay.
resultsOverexpression of TGF-beta1 leads to a markedly increased invasion potential but a reduced growth rate in BxPC3 cells. Recombinant TGF-beta1 protein increases expression of PKCalpha in BxPC3 cells, a result that we confirmed by SSH. Moreover, TGF-beta1 reduced the sensitivity of BxPC3 cells to cisplatin treatment, and this was mediated by upregulation of PKCalpha. However, blockage of PKCalpha with Gö6976 and TbetaRII with siRNA reversed the resistance of BxPC3 cells to gemcitabine, even in the presence of TGF-beta1. Immunohistochemical data show that pancreatic cancers overexpress TGF-beta1 and P-gp relative to normal tissues. In addition, TGF-beta1 expression is associated with P-gp and membranous PKCalpha expression in pancreatic cancer.
conclusionsTGF-beta1-induced drug resistance in pancreatic cancer cells was associated with PKCalpha expression. The PKCalpha inhibitor Gö6976 could be a promising agent to sensitize pancreatic cancer cells to chemotherapy.
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