MMTV-cre-mediated fur inactivation concomitant with PLAG1 proto-oncogene activation delays salivary gland tumorigenesis in mice.

Proprotein convertases are serine endoproteases implicated in the proteolytic processing of a large variety of regulatory proteins. An important role of proprotein convertases in tumorigenic processes has been suggested by various studies. In this study, the role of the proprotein convertase furin in PLAG1 proto-oncogene-induced salivary gland tumorigenesis was investigated. PLAG1 overexpression in salivary glands has previously been shown to result in salivary gland tumors in 100% of mice within 5 weeks after birth. MMTV-cre-mediated inactivation of fur without over-expression of PLAG1 caused smaller but histologically normal salivary glands. Moreover, the lymph nodes close to the salivary glands were enlarged, and histology showed that they had activated follicles. When genetic ablation of 1 or 2 alleles of fur and overexpression of the PLAG1 transgene were simultaneously achieved, a significant delay in tumorigenesis was observed. Collectively, these results suggest an important role for furin in PLAG1-induced salivary gland tumorigenesis in mice.