Morphological and biological modifications induced in a rat pancreatic acinar cancer cell line (AR4-2J) by unscheduled expression of basic fibroblast growth factors.

ABSTRACT

The role of the different basic fibroblast growth factor (bFGF) forms on the regulation of pancreatic acinar cancer cells was analyzed on the rat cell line AR4-2J. This cell line expresses bFGF receptors but does not produce bFGF. AR4-2J cells were retrovirally transfected with the wild type or with point-mutated bFGF complementary DNAs in order to obtain the expression of all the bFGF forms (clone A4), or of that of the M(r) 22,500 form (clone A3), or of that of the M(r) 18,000 form (clone A5). Each clone was less tumorigenic in nude mice than AR4-2J cells. In culture, only the coexpression of all the bFGF forms modified cell morphology (fibroblast-like) and secretory enzyme synthesis (about a 20-fold decrease of amylase and lipase). Cells expressing the high molecular weight bFGF (A3 and A4) were able to grow in serum-free medium. As for AR4-2J, exogenously added bFGF still exerted mitogenic effects on the bFGF-producing cells. These results suggest that pancreatic acinar cancer cells may respond to endogenous bFGF; furthermore, they seem very sensitive to the coexpression of the different bFGF forms which is often described in cancer cells.