TGF-beta receptors and lung cancer

Download the .pdf version of the article: "Gene expression of transforming growth factor beta receptors I and II in non-small-cell lung tumors" published by Cytokine 00 (2003), 1-8.

 

Lung cancer is one of the leading causes of cancer death in industrialized countries. The World Health Organization divides these tumors in four major categories: Squamous Cell Carcinoma, Adenocarcinoma, Large Cell Carcinoma collectively named Non-Small Cell Carcinoma (NSCC), and Small Cell Carcinoma (SCC). It has been suggested that hypo-responsiveness to Transforming Growth Factor b (TGF-beta) may be an important stage in tumor progression. The TGF-beta family of growth factors includes several isoforms (TGF-beta1, 2 and 3 in mammals) which are widely expressed in most tissues and have been shown to control a variety of cellular processes. TGF-beta biological activities include control of cell differentiation, adhesion, interaction with extra-cellular matrix as well as inhibition of epithelial cell proliferation. These are consequential to TGF-beta ligand interaction with specific cellular serine/threonine kinase receptors, the TGF-beta receptor type I (TbRI) and type II (TbRII). In non-transformed epithelial cells, TGF-beta acts as a potent growth inhibitor while in transformed cells it is known that there are various mechanisms in tumor progression that involve the TGF-beta system. These include a very tight control in vivo of TGF-beta processing and activation, and a relative inefficiency of TGF-beta signal transduction, causing a functional absence of TGF-beta responses in presence of TGF-beta ligand. In human NSC lung carcinoma cell lines TGF-beta ligand, TbRI and TbRII mRNA can be detected, but how this would relate in vivo to receptor protein expression and its cellular distribution remains to be seen. Ours previous results may suggest an altered processing pathway in TbRII production in NSC lung cancer, with an altered cellular distribution of TbRII protein, and lower gene expression of TbRII mRNA. We are currently studying TbRI and TbRII expression and functional activity in human lung tissue and in NSC lung cancer.