Role of peroxisome proliferator-activated receptor-gamma in hematologic malignancies.
Members of the nuclear receptor superfamily, including retinoic acid receptors (RARs), retinoid X receptors (RXRs), and vitamin D receptors (VDRs), are transcription factors that control many important cellular functions, and their ligands are widely used in several clinical indications. The latest family member is the peroxisome proliferator-activated receptor-gamma (PPARgamma), which is highly expressed in normal monocytes, different leukemias, and epithelial malignancies. PPARgamma ligands have been developed and signal differentiation, growth arrest, and apoptosis. PPARgamma forms heterodimers with RXR, and ligation of both receptors is required for maximal signaling. PPARgamma signaling, its expression in hematologic malignancies, and role in differentiation are discussed. Interactions of PPARgamma with X-RARalpha, protein kinase R (PKR), PTEN, and mitogen-activated protein kinase (MAPK) have been described. PPARgamma ligands have been developed for the management of diabetes, but new and more potent ligands, including triterpenoids, are being investigated as therapeutic agents for epithelial and hematologic malignancies.
Konopleva
Marina
M
Department of Blood and Marrow Transplantation, Section of Molecular Hematology and Therapy, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Andreeff
Michael
M
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D019337:Hematologic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors