Keratinocyte Transglutaminase Expression Varies in Squamous Cell Carcinomas

Type I transglutaminase (TGase I, keratinocyte or particulate transglutaminase) is a 92-kilodalton (kDa) protein expressed in abundance in cultured keratinocytes and in the hyperproliferative skin disorder psoriasis. To determine the expression of TGase I protein and mRNA, we studied tissue and established squamous carcinoma lines derived from different sources. Immunohistochemistry and Western blotting were used to detect TGase I protein with the B.C1 mouse monoclonal antibody. Only well-differentiated, skin-derived squamous carcinomas stained for TGase I. However, a precocious pattern of expression was seen overlying less-differentiated tumors. Compared to cultured human keratinocytes, squamous cell carcinoma (SCC) had many times less to 7.8 times more TGase I protein, greatest in the two most differentiated tumor lines 14–83 and ME-180. TGase I mRNA levels ranged from 0.010 to 0.00004 pg/μg total RNA by reverse transcriptase-polymerase chain reaction using an internal standard. Protein expression correlated with mRNA levels in most SOC lines. When a human TGase I promoter was isolated and used to study genomic DNA, SCC 1–83 was shown to have unique restriction enzyme fragments, including one indicative of methylation differences, also present within DNA from the KB line. These studies suggest that transcriptional control of TGase I gene expression in squamous carcinomas may be influenced both by cis elements in the promoter and by the degree of tumor squamous differentiation