The In Vitro Analysis of Biochemical Changes Relevant to Skin Carcinogenesis

Abstract

The phenotypic alterations produced in mouse skin cells during the multistage development of squamous cancer have been well documented. In normal skin, all proliferating cells are confined to the basal cell compartment where less than 10% of the cells are in S phase when pulse-labeled with DNA precursors. Two keratins, K5 (M _r 60 000) and K14 (M _r 55 000), are transcribed largely in basal cells, although the proteins persist in the upper layers (Roop et al. 1988). The commitment to differentiate is associated with the loss of proliferative potential, the commencement of suprabasal migration, and the expression of two suprabasal keratins, K1 (M _r 67 000) and K10 (M _r 59 000) in the first spinous cell layer (Roop et al. 1988). Proliferating cells do not express K1 or K10 in normal epidermis. As cells migrate into the granular cell layer, K1 and K10 transcripts diminish and the genes for filaggrin, a M _r 27 000 interfilamentous matrix protein, and loricrin, a major component of the cornified envelope, are activated and the proteins synthesized (Mehrel et al. 1990; Roop et al. 1989).