Short Communication: Expression of Human Endogenous Retrovirus-R Gene Links to Differentiation of Squamous Cells

Abstract

To investigate the biological roles of human endogenous retrovirus-R (HERV-R) in vivo, we established transgenic rats carrying the full sequence of the viral genome with control of its own long terminal repeat promoter. The Env protein was expressed on the surface of the epidermis of fetal HERV-R transgenic rats on day 10 of gestation. The epidermal Env expression disappeared by day 18 of gestation. After day 18 of gestation, the Env protein was detected in the prickle layer of the esophageal epithelium of transgenic rats. Interestingly, it was not detected in the basal layer of the epithelium, and the expression in the granular layer was weaker than in the prickle layer. These findings suggest that expression of HERV-R is linked not only to the development but also to the differentiation of squamous cells. Next, we examined alterations in the expression of the HERV-R env gene in cultured human squamous cells after exposure to all-trans retinoic acids (ATRA). The env expression was increased by ATRA in a dose-dependent manner, while the expression of transglutaminase 1 (TGM1), a terminal marker for squamous differentiation, was decreased. TGM1 is expressed in the granular layer of the squamous epithelium, and ATRA suppresses the differentiation of cultured squamous cells. Thus, these in vitro data also suggest that HERV-R expression is regulated by a mechanism closely related to the differentiation of squamous cells. This study is the first to demonstrate the association of HERV-R expression and differentiation of squamous cells.