Cell Growth & Differentiation, Vol 5, Issue 4 349-357, Copyright © 1994 by American Association of Cancer Research

ARTICLES

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

G Zhang, JD Sato, MT Herley, MW Tsang, H Ye, H Liu, T Ichimura, G Yan, WL McKeehan and JL Stevens
W. Alton Jones Cell Science Center, Lake Placid, New York 12946.

Rat kidney proximal tubule epithelial cells (RPTE) in primary culture express acidic fibroblast growth factor 1 (FGF-1). Transformation of RPTE by SV40 (SV-RPTE) suppressed FGF-1 expression but activated secretion of FGF-like factor(s). SV-RPTE conditioned medium contained growth-promoting activity for SV-RPTE and human umbilical vein endothelial cells, indicating that both autocrine and angiogenic factors were secreted. Reverse transcriptase-polymerase chain reaction and Northern analysis for various FGFs showed that only FGF-3, also known as int-2, mRNA was expressed in SV-RPTE. In addition, expression of mRNA for the heparin-binding angiogenic factor vascular endothelial growth factor (VEGF) increased dramatically in SV-RPTE. Physical characterization of the activity in the SV-RPTE conditioned medium suggested that FGF-3 and VEGF contributed the autocrine and angiogenic activities, respectively. We also investigated FGF-3 and VEGF secretion in temperature-sensitive (ts) SV40-transformed RPTE. tsSV-RPTE had transformed properties resembling those of SV-RPTE only at the permissive temperature (33 degrees C), e.g., increased growth potential and anchorage-independent growth. FGF-1 was expressed only at the nonpermissive temperature. VEGF mRNA levels and secretion of the human umbilical vein endothelial cell growth-promoting activity were reduced by switching tsSV-RPTE cells from 33 degrees to 39 degrees C. However, FGF-3 mRNA levels were not affected 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 transformation.(ABSTRACT TRUNCATED AT 250 WORDS)

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