1. ^*Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
2. ^†Life Sciences, Lawrence Berkeley National Laboratory, Berkeley, California, USA

Correspondence: Dr Norihisa Matsuyoshi, Department of Dermatology, Graduate School of Medicine, Kyoto University, 54 kawahara-cho, Shogo-in, Sakyo-ku, Kyoto 606-8317, Japan. Email: nori@kuhp.kyoto-u.ac.jp

Received 6 September 2004; Revised 8 November 2004; Accepted 29 November 2004.

Abstract

T-cadherin is a unique member of the cadherin superfamily that lacks the transmembrane and cytoplasmic domains, and is instead linked to the cell membrane via a glycosyl-phosphatidylinositol anchor. We previously reported that T-cadherin was specifically expressed on the basal keratinocytes of the epidermis, and the expression of T-cadherin was significantly reduced in invasive cutaneous squamous cell carcinoma (SCC) and in the lesional skin of psoriasis vulgaris. In this study, to obtain an insight into the role of T-cadherin in keratinocytes, we used transfection methods and examined the effect of overexpression or knockdown of T-cadherin in immortalized keratinocyte cell lines derived from SCC. T-cadherin overexpressed cells showed clearly reduced cell proliferation, but the influence of cell–cell adhesiveness and cell mobility was not detected. Using a tetracycline-regulated expression system, we also confirmed that the suppression of cell proliferation was dependent on the expression level of T-cadherin. Cell cycle analysis demonstrated that over expression of T-cadherin induced a delay in the G₂/M phase. Our findings suggest that T-cadherin acts as an endogenous negative regulator of keratinocyte proliferation and its inactivation is the cause for keratinocyte hyperproliferation in SCC or in psoriasis vulgaris.