OVEREXPRESSION OF PROGRANULIN INCREASES CELLS IN GROWTH PHASE BUT IS INSUFFICIENT TO INDUCE SKIN TUMOR FORMATION

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 re- sult 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 us- ing 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 ob- served no significant difference in the incidence of spontaneously occurring and chemically in- duced skin tumors between the transgenic and wild-type mice. These results suggest that over- expression of PGRN alone is insufficient to cause cancerous transformation of keratinocytes.