Malignant transformation results from genetic changes interfering with a cellular signaling network that in healthy cells controls processes of differentiation, proliferation and death to maintain homeostasis. Understanding of the role of key regulators in this network and their interactions is an important step in creation of anti-tumor therapies. Proteins Myb, Fos, Jun and retinoid receptors belong to this group and we wish to determine the role they play in regulation of differentiation and prolifera tion of leukemic cells. We have showed previously that the retinoic acid receptor (RAR) and its dimerization partner (RXR) could act in a dominant, ligand-dependent fashion to suppress leukemic transformation by the v-myb oncogene. Additional preliminary data now suggest that the Jun transcription factor may regulate the differentiation of v-myb-transformed BM2 cells via activation of endogenous retinoic acid receptor pathways. To test this hypothesis directly, we propose to address the following specif

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