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Transforming growth factor (TGF)beta inhibits normal epithelial cell proliferation. A decreased expression of TGFbeta receptors (TbetaR) has been associated with loss of TGFbeta sensitivity and enhanced tumor progression in many types of cancer. Although lung cancer is one of the leading causes of cancer death, a comparative analysis of TbetaR mRNA and protein expression in non-small-cell (NSC) lung tumors has not been performed. Lung tumor tissues and control non-lesional lung tissues were obtained from 17 patients undergoing thoracotomy for primary NSC lung tumors in clinical stage II. Each tissue sample was studied for TbetaRI and TbetaRII mRNA and immunoreactive protein expression, using a semi-quantitative reverse transcription-PCR method, and a quantitative immunohistochemistry method, respectively. TbetaRI protein expression was higher in tumors than in controls (p=0.0005) and a similar trend was present at the mRNA level. TbetaRII protein expression was not significantly different between tumors and controls, however an intense peri-nuclear staining for TbetaRII was observed in several tumor cells. TbetaRII mRNA levels were lower in tumors than in controls (p=0.005) and an inverse relation between TbetaRII mRNA and protein expression was detected in tumors (p=0.0013). Our findings suggest an altered function of the TbetaR system in NSC lung cancer.