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Transglutaminase type 1 (TGase 1) is a member of a class of enzymes that catalyze the cross-linking of proteins, a characteristic feature of epidermal differentiation and squamous metaplasia. The role of TGase 1 has been extensively studied in epidermis but not in the lung. Using a polyclonal anti-TGase 1 antibody prepared in our laboratory (TGase-lac), TGase 1 expression in normal bronchial epithelium, bronchial preinvasive lesions, and lung cancer was characterized. The specificity of the antibody was confirmed by the presence in squamous differentiated bronchial cells of specific 106-kD and 92-kD bands by Western blotting. In addition, immunohistochemistry displayed a recognized pattern of labeling in both normal and tumor cells beneath the cytoplasmic membrane and within the cytosol. TGase 1 was shown to be expressed by cells from bronchial epithelium and bronchial preinvasive lesions, strongly expressed in most non-small-cell lung cancer tumor cells and in apoptotic bodies, but weakly expressed in small-cell lung cancer. The distribution of TGase 1 mRNA correlated with the immunohistochemical profile. These observations suggest that TGase 1 expression is a normal feature of bronchial epithelium and is linked to the process of squamous differentiation occurring in preinvasive lesions. Its role in lung cancer remains to be clarified.
In vivo squamous metaplasia of bronchial mucosa is induced by carcinogens contained in tobacco smoke, as well as by severe vitamin A deficiency, and is considered to be the initial step in the multistep carcinogenic process that leads to the development of squamous cell carcinoma (1). The squamous phenotype of cells from bronchial preinvasive lesions is similar to the phenotype of differentiated keratinocytes, as illustrated by the sequential induction of the genes involved in the formation of the cornified cell envelope (CE) (2). This layer of enucleated shells is the characteristic feature of epidermal differentiation, and it contains a compact network of proteins whose structure is strongly influenced by transglutaminase (TGase). TGase is a key enzyme that catalyzes the cross-linking between the CE-precursors. Initially, it was thought to be expressed only in the skin epidermis; however, Northern as well as Western blotting analyses have indicated that TGase 1 is also expressed in tissues containing simple epithelia, such as liver and kidney. Some investigators have reported the expression of TGase 1 in cultured human...