Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells

G. Anumanthan, S. K. Halder, H. Osada, T. Takahashi, P. P. Massion, D. P. Carbone, P. K. Datta

Research output: Contribution to journalArticle

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Abstract

Members of the transforming growth factor-β (TGF-β) family regulate a wide range of biological processes including cell proliferation, migration, differentiation, apoptosis, and extracellular matrix deposition. Resistance to TGF-β-mediated tumour suppressor function in human lung cancer may occur through the loss of type II receptor (TβRII) expression. In this study, we investigated the expression pattern of TβRII in human lung cancer tissues by RT-PCR and Western blot analyses. We observed downregulation of TβRII in 30 out of 46 NSCLC samples (65%) by semiquantitative RT-PCR. Western blot analyses with tumour lysates showed reduced expression of TβRII in 77% cases. We also determined the effect of TβRII expression in lung adenocarcinoma cell line (VMRC-LCD) that is not responsive to TGF-β due to lack of TβRII expression. Stable expression of TβRII in these cells restored TGF-β-mediated effects including Smad2/3 and Smad4 complex formation, TGF-β-responsive reporter gene activation, inhibition of cell proliferation and increased apoptosis. Clones expressing TβRII showed reduced colony formation in soft-agarose assay and significantly reduced tumorigenicity in athymic nude mice. Therefore, these results suggest that reestablishment of TGF-β signalling in TβRII null cells by stable expression of TβRII can reverse malignant behaviour of cells and loss of TβRII expression may be involved in lung tumour progression.

Original languageEnglish (US)
Pages (from-to)1157-1167
Number of pages11
JournalBritish Journal of Cancer
Volume93
Issue number10
DOIs
StatePublished - Nov 4 2005

Fingerprint

Transforming Growth Factors
Lung Neoplasms
Nude Mice
Western Blotting
Cell Proliferation
Apoptosis
Biological Phenomena
Null Lymphocytes
Neoplasms
Polymerase Chain Reaction
Reporter Genes
Sepharose
Transcriptional Activation
Cell Movement
Extracellular Matrix
Down-Regulation
Clone Cells
Cell Line
Lung

Keywords

  • Apoptosis
  • NSCLC
  • RT-PCR
  • TGF-β1
  • Tumorigenicity
  • TβRII

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Anumanthan, G., Halder, S. K., Osada, H., Takahashi, T., Massion, P. P., Carbone, D. P., & Datta, P. K. (2005). Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells. British Journal of Cancer, 93(10), 1157-1167. https://doi.org/10.1038/sj.bjc.6602831

Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells. / Anumanthan, G.; Halder, S. K.; Osada, H.; Takahashi, T.; Massion, P. P.; Carbone, D. P.; Datta, P. K.

In: British Journal of Cancer, Vol. 93, No. 10, 04.11.2005, p. 1157-1167.

Research output: Contribution to journalArticle

Anumanthan, G, Halder, SK, Osada, H, Takahashi, T, Massion, PP, Carbone, DP & Datta, PK 2005, 'Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells', British Journal of Cancer, vol. 93, no. 10, pp. 1157-1167. https://doi.org/10.1038/sj.bjc.6602831
Anumanthan G, Halder SK, Osada H, Takahashi T, Massion PP, Carbone DP et al. Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells. British Journal of Cancer. 2005 Nov 4;93(10):1157-1167. https://doi.org/10.1038/sj.bjc.6602831
Anumanthan, G. ; Halder, S. K. ; Osada, H. ; Takahashi, T. ; Massion, P. P. ; Carbone, D. P. ; Datta, P. K. / Restoration of TGF-β signalling reduces tumorigenicity in human lung cancer cells. In: British Journal of Cancer. 2005 ; Vol. 93, No. 10. pp. 1157-1167.
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