Enhancing effects of fibroblast growth factor on the proliferation of salivary gland carcinoma cells and salivary gland carcinogenesis

The proliferation of mouse submandibular gland carcinoma YT-12 cells was st imulated by endothelial cell growth factor (ECGF)/bovine brain-derived acid ic fibroblast growth factor (aFGF) and recombinant human aFGF. To determine whether aFGF was capable of modifying salivary gland carcinogenesis, the e ffect of brain-derived aFGF was examined in vivo. Mice in Groups 1 and 2 we re injected with 9,10-dimethyl-1,2-benzanthracene (DMBA) into the left subm andibular gland, and then Group 1 mice received bovine brain-derived aFGF a nd Group 2 mice received vehicle subcutaneously for 10 weeks. Group 3 and 4 mice received either bovine brain-derived aFGF or vehicle only. Sixteen we eks after the start of the experiment, the incidence of submandibular gland carcinomas in Group 1 was significantly greater than that in Group 2, Immu nohistochemical study indicated that ducts in the normal submandibular glan ds and carcinomas showed positive staining with anti-aFGF antibody. Immunob lot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis r evealed the expression of aFGF in these tissues. FGF receptor (FGFR)-1 and FGFR-4 were detectable in the mouse submandibular glands and carcinomas. Th ese findings suggest that bovine brain-derived aFGF stimulates the prolifer ation of submandibular gland carcinoma cells and promotes mouse submandibul ar gland carcinogenesis.