A Novel Mechanism of PPARgamma Regulation of TGFbeta1: Implication in Cancer Biology.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) and retinoic acid X-receptor (RXR) heterodimer, which regulates cell growth and differentiation, represses the TGFbeta1 gene that encodes for the protein involved in cancer biology. This review will introduce the novel mechanism associated with the inhibition of the TGFbeta1 gene by PPARgamma activation, which regulates the dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of TGFbeta1 by PPARgamma activators can be applied for treating TGFbeta1-induced pathophysiologic disorders such as cancer metastasis and fibrosis. In this article, we will discuss the opposing effects of TGFbeta on tumor growth and metastasis, and address the signaling pathways regulated by PPARgamma for tumor progression and suppression.
Lee
Chang Ho
CH
Department of Pharmacology, Institute of Biomedical Science, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
Kim
Hyung Don
HD
Shin
Sang Mi
SM
Kim
Sang Geon
SG