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

51 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    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