Session: SUN 303-321-Cancer in Endocrine Tissues
Bench to Bedside
Poster Board SUN-315
The aim of this study was to assess the effect of 20-hydroxylated (20-HETE) and epoxygenated (11,12-EET and 14,15-EET) metabolites in the proliferation rate of Mouse Pheochromocytoma Cells 3 (MPC3) and to analyze the expression 20-hydroxylases and epoxygenases in murine and human pheochromocytoma.
CYP expression was analyzed by Western Blot and/or PCR in MPC3 cell culture, murine tumors generated by s.c. injection of MPC3 cells, and frozen human tumor samples of sporadic (n=6) or familial [von Hippel Lindau disease (VHL) (n=5), Multiple Endocrine Neoplasia (MEN 2A) (n=3) or Paraganglioma type 4 (PGL4) (n=2)] pheochromocytomas and paragangliomas.
MPC3 cells were incubated with 20-HETE (20uM) or 11,12-EET or 14,15-EET (10nM for both) in low serum medium. 48h incubation resulted in an increase in cell number (increase over control: 20-HETE 64%, n.s.; 11,12-EET 99%, p<0.05; 14,15-EET 141%, p<0.01).
CYP4A12 (murine 20-hydroxylase), CYP2C29, 2C38 y 2C44 (murine epoxygenases) were detected in murine tumors; yet none of them was found in MPC3 cell culture.
In human samples, isoform expression was related to the genetic background of the tumor: CYP2J2 was low in all samples except in MEN2A. CYP4A11 and 4F2 were present in all samples, being the CYP/tubulin ratio significantly different in PGL4 vs. sporadic for CYP4A11 (0.94±0.06 vs. 0.25±0.14; p<0.05) and in MEN2A vs. VHL for CYP4F2 (1.99±0.28 vs. 1.19±0.18; p<0.05).
Our results demonstrate that these CYP- derived arachidonic acid metabolites have an impact on proliferation in MPC3 cell culture. In addition these CYPs are expressed both in human and murine tumors. Altogether, these results point to a contribution of these metabolites to pheochromocytoma biology.
Nothing to Disclose: CEC, MCF, GS, AV, MBB, PP, SN
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