Functional Characterization and Molecular Mechanism of a FABP5-PPARγ-VEGF Signaling Axis Promoting T

来源 :1st International Prostate Cancer Symopsium-2015、1st Interna | 被引量 : 0次 | 上传用户:sdgvf43g43g3
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  To study how the cancer-promoting signals are transmitted through thisFABP5-PPARγ-VEGF signalling axis, we first investigated the tumoriegnicity-promoting role of PPARγ in prostatic cancer.Suppression of PPARγ inhighly malignant prostatic cancer cells produced a significant reduction in the malignant properties of the cancer cells both in vitro and in vivo.The results also suggested that FABP5 promoted VEGF expression and hence facilitated angiogenesis through PPARγ which was activated by thestimulation of the fatty acids transported by FABP5.Further investigations showed that PPARγ up-regulated VEGF expression through acting with the PPAR-responsive elements in VEGF promoter region in prostatic cancer cells.Although androgen can modulate VEGF expression through Sp1/Sp3 binding site on VEGF promoter in androgen-dependent prostatic cancer cells, this route, disappeared as the cells lost their androgen dependency;was replcaced by the FABP5-PPARγ-VEGF signaling axis.These results suggested that the FABP5-PPARγ-VEGF signaling axis, rather than androgen modulated route, may be a more important novel therapeutic target for angiogenesis-suppression in the treatment of castration resistant prostatic cancer.
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