Diabetologie und Stoffwechsel 2016; 11 - LB10
DOI: 10.1055/s-0036-1584104

Mitogenic response of human carcinoma cells to the liver-derived hormone FGF21

L Berti 1, 2, B Rädle 2, HU Häring 1, 2, 3, M Hrab((ebrevis)) de Angelis 2, H Staiger 1, 2, 3
  • 1Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
  • 2Institute of Experimental Genetics, Helmholtz Center Munich, German Research Center for Enviromental Health, Neuherberg, Germany
  • 3University Hospital, Tübingen, Germany

Background and aims: Epidemiologically, type-2 diabetes mellitus (T2D) is associated with various cancer types. The factors linking these diseases are not understood yet. Since plasma FGF21 levels are increased in metabolic diseases, we asked whether FGF21 promotes tumor cell proliferation.

Methods: Breast adenocarcinoma- (MCF7), prostate adenocarcinoma- (PC3), hepatocellular carcinoma- (HepG2) and, for control, non-transformed breast epithelial (MCF10a) cells were treated with recombinant human FGF21 (rhFGF21). Cell viability/cell number, DNA content, cellular protein and RNA were analyzed.

Results: Treatment of MCF7, PC3, and MCF10a cells with increasing concentrations of rhFGF21 induced a modest but significant increase in cell viability/cell number (p < 0.001, p < 0.01 and p < 0.05), measured by XTT assay. No effect was seen in HepG2 cells. DNA amount was significantly increased in all cell lines. All cell lines expressed FGFR1, FGFR4 and FRS2 encoding surface receptors/receptor substrates involved in FGF21 signaling. A clear dose-response was seen in PC3 cells. In these cells, acute stimulation with rhFGF21 induced ERK1/2 phosphorylation. The expression of immediate early genes (FOS, JUN) and of IRS1 was significantly elevated within 4h. Furthermore, a trend for increase in SLC2A1 and HK2 expression was observed within 24h of rhFGF21 treatment.

Conclusions: Our data show that FGF21 treatment of human carcinoma cells increases cell viability and proliferation probably via the MAPK pathway and induction of mitogenic and trophic genes. Thus, the hepatokine FGF21 elevated in metabolic diseases may represent a contributor to T2D-related tumor progression.