In Vivo Transglutaminase Type 1 Expression in Normal Lung, Preinvasive Bronchial Lesions, and Lung Cancer

Abstract

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.

Transglutaminase-1 Regulates Renal Epithelial Cell Proliferation through Activation of Stat-3

“…3A). TGase-1 antibody recognized two isoforms of TGase-1, ϳ106 and ϳ92 kDa, which are consistent with a previous observation in normal human bronchial cells (4). The ϳ92 kDa band is considered to be the membrane-associated TGase, whereas the ϳ106 kDa band is the soluble/cytosolic form of the proteins (4).…”

“…of three independent experiments conducted in triplicate and expressed as -fold increase relative to controls. *, p Ͻ 0.05. mouse RPTC, we examined the expression of TGase-1, -5, and -7 using immunoblot analysis, because TGase-1 and -5 have been identified in the kidney and TGase-7 is widely expressed in mammalian tissues (1,3,4). However, we only detected TGase-1 in mouse RPTC.…”

Tissue transgluaminase 2 expression in meningiomas

“…Based on these findings in gliomas, we further investigated the levels of TG2 expressed in meningiomas and its potential as a target to decrease resistance to apoptosis.. In addition to glioblastomas, elevated levels of TG2 have been found in several neoplasms including lung [16] and breast [17] cancers, suggesting a significant role for TG2 in tumorigenesis. High expression levels of TG2 have also been associated with resistance to chemotherapy in multiple tumor cell lines [18,19].…”

Enhanced Peritoneal Ovarian Tumor Dissemination by Tissue Transglutaminase

“…We previously reported that TG2 mRNA expression is upregulated in transformed ovarian epithelial cells and tumors compared with normal ovarian surface epithelial cells (15). Other reports link TG2 to epithelial cancers, particularly breast (16), pancreatic (17), and non-small cell lung cancer (18). In breast cancer cells, membrane-bound TG2 has kinase activity and phosphorylates the insulin-like growth factor-binding protein-3 (19) and the enzyme is overexpressed in drug-and radiationresistant breast cancer cells (20,21).…”