ArticleInternational journal of radiation oncology, biology, physics2007
Inhibition of transforming growth factor-beta signaling in normal lung epithelial cells confers resistance to ionizing radiation.
Article in International journal of radiation oncology, biology, physics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- TGFβ Inhibition during Radiotherapy Enhances Immune Cell Infiltration and Decreases Metastases in Ewing Sarcoma.Cancer research communications · 2025Article
- Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation.Journal of cell communication and signaling · 2019Review
- Inhibiting TGFβ1 has a protective effect on mouse bone marrow suppression following ionizing radiation exposure in vitro.Journal of radiation research · 2013Article
- Na,K-ATPase subunits as markers for epithelial-mesenchymal transition in cancer and fibrosis.Molecular cancer therapeutics · 2010Article
- Role of Radiation-induced TGF-beta Signaling in Cancer Therapy.Molecular and cellular pharmacology · 2009Article
- Biologically conformal treatment: biomarkers and functional imaging in radiation oncology.Future oncology (London, England) · 2008Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo address the functional role of radiation-induced transforming growth factor-beta (TGF-beta) signaling in a normal epithelial background, we selected a spontaneously immortalized lung epithelial cell line derived from the normal lung tissue of a dominant-negative mutant of the TGF-beta RII (DeltaRII) transgenic mouse that conditionally expressed DeltaRII under the control of the metallothionein promoter (MT-1), and assessed this cell line's response to radiation. METHODS AND MATERIALS: A spontaneously immortalized lung epithelial cell culture (SILECC) was established and all analyses were performed within 50 passages. Colony-forming and terminal transferase dUPT nick end labeling (TUNEL) assays were used to assess clonogenic inhibition and apoptosis, respectively. Western-blot analysis was performed to assess the kinetics of p21, bax, and RII proteins. Transforming growth factor-beta-responsive promoter activity was measured using dual-luciferase reporter assay.
resultsExposure to ZnSO(4) inhibited TGF-beta signaling induced either by recombinant TGF-beta1 or ionizing radiation. The SILECC, treated with either ZnSO(4) or neutralizing antibody against TGF-beta, showed a significant increase in radio-resistance compared to untreated cells. Furthermore, the expression of DeltaRII inhibited the radiation-induced up-regulation of the TGF-beta effector gene p21(waf1/cip1).
conclusionsOur findings imply that inhibition of radiation-induced TGF-beta signaling via abrogation of the RII function enhances the radio-resistance of normal lung epithelial cells, and this can be directly attributed to the loss of TGF-beta signaling function.
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