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 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)
Zhang
G
G
W. Alton Jones Cell Science Center, Lake Placid, New York 12946.
Sato
J D
JD
Herley
M T
MT
Tsang
M W
MW
Ye
H
H
Liu
H
H
Ichimura
T
T
Yan
G
G
McKeehan
W L
WL
Stevens
J L
JL
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D006358:Hot Temperature; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000503:physiopathology*; D008222:Lymphokines / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D013539:Simian virus 40 / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; C489199:Fgf3 protein, rat; D051518:Fibroblast Growth Factor 3; D006133:Growth Substances; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors