Progranulin (PGRN), a multifunctional secreted growth factor, is highly expressed in various types of human cancers. However, it is still unknown whether upregulation of PGRN is a cause or a result of cancerous transformation. To assess the consequences of enhanced PGRN expression in vivo, we generated transgenic mice in which PGRN is specifically expressed in keratinocytes using the Cre/lox system. PGRN overexpression in the epidermis promoted the entry of basal cells to the proliferation phases, as revealed by Ki-67 immunostaining, but was insufficient to facilitate it to the mitotic phase, as revealed by phosphohistone H3 immunoreactivity. Accordingly, we observed no significant difference in the incidence of spontaneously occurring and chemically induced skin tumors between the transgenic and wild-type mice. These results suggest that overexpression of PGRN alone is insufficient to cause cancerous transformation of keratinocytes
