The Ecdysteroids' Effects in the Control of Cell Proliferation and Differentiation

Abstract

In insects, the steroid hormone 20-hydroxyecdysone (20E) plays a critical role in the control of cellular proliferation and differentiation. The cells show different responses to 20E according to the concentration to which they are exposed. The 20E at 10−7 M induces an inhibition of growth by a blockage of cells in G2/M and long term morphological transformation. The establishment of 20E responsive cell lines provided potentialities to investigate the molecular events responsible for these cellular responses as well as theirs dynamics through the cell cycle. In the Plodia interpunctella IAL-PID2 cell line, an optimal period of sensitivity of cells to 20E, in inducing G2/M arrest, was preferentially located at the transition S/G2 with a high induction of EcR, USP and HR3 mRNAs and a decrease in the expression level of B-cyclin at the end of G2 phase. On the other hand, the 20E-induced cytoskeleton rearrangement was accompanied by a redistribution of cytoplasmic microtubules which was concomitant with an increase in the β tubulin mRNA amount. The use of RNAi technique allowed to demonstrate that inhibiting the induction of EcR, USP and HR3 suppressed the 20E effects on the synthesis of B-cyclin and β tubulin then consequently prevented the arrest and the transformation òf IAL-PID2 cells. This functional approach revealed that 20E was able to regulate the cellular differentiation and proliferation by acting on regulators of cell cycle and cytoskeleton proteins through a genomic signaling pathway involving EcR, USP and HR3.