Carcinogenesis Advance Access published online on March 19, 2007
Carcinogenesis, doi:10.1093/carcin/bgm059
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Mst1, RanBP2, and eIF4G are new markers for in vivo PI3K activation in murine and human prostate
Experimental Therapeutics Programme, Spanish National Cancer Centre (CNIO), C/Melchor Fernandez Almagro 3, 28029 Madrid, Spain
# Molecular Pathology Programme, Spanish National Cancer Centre (CNIO), C/Melchor Fernandez Almagro 3, 28029 Madrid, Spain
* Corresponding author: Amancio Carnero, Experimental Therapeutics Programme, Spanish National Cancer Centre (CNIO), C/Melchor Fernandez Almagro 3, 28029 Madrid, Spain (E-mail: acarnero{at}cnio.es)
Phosphatidylinositol 3-kinases (PI3Ks) constitute important regulators of signaling pathways. The PIK3CA gene encoding the p110-alpha catalytic subunit represents one of the highly mutated oncogenes identified in human cancer. Here we report new markers for in vivo PI3K activation in prostate. To that end, we used a transgenic mouse line, which expresses a constitutively active p110-alpha subunit in the epithelial cells of the prostate. The activity of the PI3K pathway in the prostate was proven by assessing the phosphorylation of the PI3K direct target AKT1 and of the mTOR-target eukaryotic translation factor 4G (eIF4G). To establish also transcriptional ("late") targets of the PI3K pathway, we tested two genes, Mst1 and RanBP2, which we recently described as transcriptional targets of the growth factor PDGF-B. We show that the levels of both proteins are elevated in transgenic animals. Additionally, we describe that the phosphorylation of AKT and eIF4G, as well as the elevation of the Mst1 and RanBP2 protein levels, can be inhibited in vivo in transgenic animals by the PI3K inhibitor LY294002. Finally, we performed human tissue microarray experiments with the four markers. Since they define overlapping but not identical subsets of the tested tissue panel, a combination of all four markers might lead to a more accurate diagnosis of the status of the PI3K signaling cascade in cancer patients.
Received December 15, 2006; revised March 6, 2007; accepted March 9, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  O. Renner, C. Blanco-Aparicio, M. Grassow, M. Canamero, J. F.M. Leal, and A. Carnero Activation of Phosphatidylinositol 3-Kinase by Membrane Localization of p110{alpha} Predisposes Mammary Glands to Neoplastic Transformation Cancer Res., December 1, 2008; 68(23): 9643 - 9653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Jang, S.-J. Yang, S. Srinivasan, and K. Ye Akt Phosphorylates MstI and Prevents Its Proteolytic Activation, Blocking FOXO3 Phosphorylation and Nuclear Translocation J. Biol. Chem., October 19, 2007; 282(42): 30836 - 30844. [Abstract] [Full Text] [PDF]
|
|