ABSTRACT
Objective: To study the mRNA expression in TGF-β1 signaling transduction pathways during the differentiation of acute promyelocytic leukemia (APL) induced by all-transretinoic acid (ATRA). Methods: The mRNA expressions of TGF-β1, TGF-βR I, TGF-βR II, Smad 2, Smad 3, Smad 4, and Smad 7 of human APL cell line NB4 were analyzed using a real-time fluorogentic quantitative-polymerase chain reaction (RFQ-PCR) assay after treatment with ATRA. The locations of PML-RARα fusion protein and Smad3 protein in NB4 cells were determined by confocal microscopy. Results: The mRNA expression levels of TGF-β1, TGF-βR I, TGF-βR II, Smad 2, Smad 3, Smad 4, and Smad 7 increased gradually during the NB4 cells' differentiation induced by ATRA. Their expression reached the peak at 48 h or 72 h and then declined gradually. But there was no significant difference in the dehydrated alcohol-treated group (control). PML-RARα fusion protein and Smad 3 protein were co-localized in NB4 cells. Conclusion: TGF-β1 signaling transduction pathways are closely related with NB4 cells' differentiation. ATRA can up-regulate the mRNA expression levels involved in the signaling transduction pathway. PML-RARα fusion protein is apt to bind with Smad 3 protein.