STABLE AND TEMPERATURE-SENSITIVE TRANSFORMATION OF RAT-KIDNEY EPITHELIAL-CELLS SUPPRESSES EXPRESSION OF ACIDIC FIBROBLAST GROWTH-FACTOR-1 BUT ACTIVATES SECRETION OF FIBROBLAST GROWTH-FACTOR-3 (INT-2) AND VASCULAR ENDOTHELIAL GROWTH-FACTOR

Rat kidney proximal tubule epithelial cells (RPTE) in primary culture express acidic fibroblast growth factor 1 (FGF-1). Transformation of R PTE by SV40 (SV-RPTE) suppressed FGF-1 expression but activated secret ion of FGF-like factor(s). SV-RPTE conditioned medium contained growth -promoting activity for SV-RPTE and human umbilical vein endothelial c ells, indicating that both autocrine and angiogenic factors were secre ted. Reverse transcriptase-polymerase chain reaction and Northern anal ysis for various FCFs showed that only FGF-3, also known as int-2 mRNA was expressed in SV-RPTE. In addition, expression of mRNA for the hep arin-binding angiogenic factor vascular endothelial growth factor (VEG F) increased dramatically in SV-RPTE. Physical characterization of the activity in the SV-RPTE conditioned medium suggested that FGF-3 and V EGF contributed the autocrine and angiogenic activities, respectively. We also investigated FGF-3 and VEGF secretion in temperature-sensitiv e (ts) SV40-transformed RPTE. tsSV-RPTE had transformed properties res embling those of SV-RPTE only at the permissive temperature (33 degree s C), e.g., increased growth potential and anchorage-independent growt h. FGF-1 was expressed only at the nonpermissive temperature. VEGF mRN A levels and secretion of the human umbilical vein endothelial cell gr owth-promoting activity were reduced by switching tsSV-RPTE cells from 33 degrees to 39 degrees C. However, FGF-3 mRNA levels were not affec ted significantly by the temperature switch suggesting that activation of VEGF and FGF-3 occurs through different mechanisms. These results indicate that FGF-1 expression in RPTE is suppressed by SV40 transform ation. However, secretion of the angiogenic factor VEGF and formation of a new FGF-like autocrine loop through activation of FGF-3 expressio n may contribute to the transformation of renal epithelial cells.