Localization and Significance of γ-Glutamyltranspeptidase in Normal and Neoplastic Mouse Skin

Abstract

The suggestion that elevated γ-glutamyltranspeptidase (GGT) activity could be a marker for hepatic neoplasia has prompted us to investigate the role of this enzyme in normal and neoplastic mouse skin. In normal skin, as determined histochemically with N -(γ-l-glutamyl)-4-methoxy-2-naphthylamide as substrate, GGT was found only in the lower epithelium of growing hair follicles. GGT activity was never detected in the interfollicular epidermis of 1-day-old prenatal, newborn, or adult skin. Whole-skin enzyme activity measured biochemically, with l-γ-glutamyl- p -nitroanilide as substrate, was elevated about 9-fold during periods of hair growth. GGT activity rose and then fell abruptly as the mice progressed through the growing phase and then the resting phase of the hair growth cycle. Skin tumors were induced by initiation with 7,12-dimethylbenz[ a ]anthracene followed by promotion with 12- O -tetradecanoylphorbol-13-acetate. Histochemically, GGT was not present in eight benign papillomas examined. However, single epithelial cells, islands of epithelial cells, and/or follicle-like structures were intensely GGT positive in seven of eight malignant squamous carcinomas examined. The association of GGT activity with normal hair growth and its presence in squamous carcinomas raises the following interesting possibilities: ( a ) aberrant gene activation in malignant interfollicular epidermis; ( b ) a recruitment of follicular cells by invasive malignant interfollicular epidermis; ( c ) a follicular origin for the GGT-positive carcinoma.