1. ¹Department of Surgery and Cancer Biology, Division of Surgical Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 1161, 21st Avenue South, A 3310C MCN, Nashville, TN 37232, USA
2. ²Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan
3. ³Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
4. ⁴Hematology/Oncology Division, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

Correspondence: Dr PK Datta, E-mail: pran.datta@vanderbilt.edu

Received 3 May 2005; Revised 25 August 2005; Accepted 20 September 2005; Published online 25 October 2005.

Abstract

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