092 Ectopic Expression of c-Myc in Murine Skin Affects the Hair Growth Cycle and Induces Sebaceous Gland Enlargement

J.J. Bull1, S. Müller-Röver2, C.M.T. Chronnell1, I.A. McKay1, S. Pelengaris3 and M.P. Philpott1. Centre for Cutaneous Research, St Bartholomew’s and the Royal London School of Medicine and Dentistry, Queen Mary College, University of London UK1. University Hospital Eppendorf, University of Hamburg, Germany2. Biological Sciences, University of Warwick, Coventry, UK3.

The mammalian hair follicle is a highly dynamic skin appendage that undergoes repeated cycles of growth and regression involving closely co-ordinated cell proliferation, differentiation and apoptosis. The transcription factor c-Myc has been strongly implicated in these processes in many tissues. c-Myc overexpression in transgenic mice has been shown to stimulate hyperproliferation and disrupt terminal differentiation of suprabasal keratinocytes in the epidermis (Pelengaris et al, 1999) and promote human keratinocyte stem cell differentiation in vitro (Gandarillas et al 1997). Recently we have reported that in human hair follicles, c-Myc expression in the outer root sheath is restricted to the putative stem cell compartment and have suggested that c-Myc may be involved in regulating cell fate within this region. In this study we have investigated the effects of c-Myc overexpression on the hair cycle and hair phenotype of transgenic mice, in which c-Myc activity can be reversibly induced by expression of c-Myc- ER™ (Pelengaris et al, 1999). Topical application of 4-hydroxytamoxifen (4OHT) was used to induce c- Myc-ER™ activity in dorsal skin of transgenic mice. Wild-type and transgenic mice were treated with 4OHT twice weekly for 7 weeks. The hair growth cycle stage of transgenic and wild-type mouse skin was then characterised. Alkaline phosphatase and oil red O staining were used to distinguish the dermal papilla and sebaceous gland respectively. In 4OHT treated c-Myc-ER™ transgenic mice, normal synchronised hair cycling was deregulated, with hair follicles at various stages of the cycle. In contrast, all hair follicles were in telogen in wild-type mice. Moreover, sebaceous glands were enlarged in 4OHT-treated c-Myc-ER™ transgenic mice. These data suggest c-Myc affects hair follicle cycling and sebaceous gland growth.