Polycomb group proteins Bmi-1 is the core subunits of the PRC1 complex,and also plays important roles in the regulation of neural development. This review introduces the construction of Bmi-1 and the recent study for Bmi-1 in the nervous system development and tumor generation. The important roles of Bmi-1 for sustain of the neural stem cell proliferation,regulation mechanism of neural development and tumor generation are discussed.
Mammals have three genes with homology to the hh gene.These comprise Sonic hedgehog(Shh),Indian hedgehog(Ihh),and Desert hedgehog(Dhh).Shh has been shown to play a crucial role in embryogenesis and the development of ectoderm.Shh has the great relationship with the forming all the system.Shh-Patched-Smoothened signal pathway will lead the embryogenesis in the normal way.Otherwise,the abnormal embryogenesis,malformation,and tumor will be happened.
The effects of Sonic hedgehog(Shh) signaling pathway activation on S-type neuroblastoma(NB) cell lines and its role in NB tumorigenesis were investigated.Immunohistochemistry was used to detect the expression of Shh pathway components— Patched1(PTCH1) and Gli1 in 40 human primary NB samples.Western blotting and RT-PCR were used to examine the protein expression and mRNA levels of PTCH1 and Gli1 in three kinds of S-type NB cell lines(SK-N-AS,SK-N-SH and SHEP1),respectively.Exogenous Shh was administrated to activate Shh signaling pathway while cyclopamine was used as a selective antagonist of Shh pathway.S-type NB cell lines were treated with different concentrations of Shh or/and cyclopamine for different durations.Cell viability was measured by using MTT method.Apoptosis rate and cell cycle were assayed by flow cytometry.The xenograft experiments were used to evaluate the role of Shh pathway in tumor growth in immunodeficient mice.High-level expression of PTCH1 and Gli1 was detected in both NB samples and S-type NB cell lines.Cyclopamine decreased the survival rate of the three cell lines while Shh increased it,and the inhibition effects of cyclopamine could be partially reversed by shh pre-treatment.Cyclopamine induced the cell apoptosis and the cell cycle arrest in G0/G1 phase,while Shh induced the reverse effects and could partially prevent effects of cyclopamine.Cyclopamine could also inhibit the growth of NB in vivo.Our studies revealed that activation of the Shh pathway is important for survival and proliferation of S-type NB cells in vivo and in vitro through affecting cell apoptosis and cell cycle,suggesting a new therapeutic approach to NB.
