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The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1.
Oncogene. 2009 Jun 25; 28(25):2406-18.O

Abstract

PIK3CA, which codes for the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), is implicated as an oncogene. Despite importance of PIK3CA in cancer, little is known about what drives up its expression in tumor cells. We recently characterized the PIK3CA promoter and reported that it is transcriptionally silenced by the tumor suppressor protein p53. In the present study, we demonstrate that PIK3CA can be induced by the oncogenic transcription factor Y-box binding protein-1 (YB-1). Three YB-1-responsive elements were identified on the PIK3CA promoter using chromatin immunoprecipitation and electrophoretic mobility shift assays. Interestingly, silencing YB-1 with siRNA in models of basal-like breast cancer decreased p110alpha protein levels regardless of whether PIK3CA was wild type, amplified or mutated. This decrease in p110alpha led to a reduction in PI3K activity and the downstream signaling primarily through p90 ribosomal S6 kinase and S6 ribosomal protein. Disruption in PIK3CA-dependent signaling suppressed cellular invasion correlative with loss of urokinase plasminogen activator (uPA). Similarly, silencing YB-1 suppressed invasion and uPA production however this was reversible through the introduction of constitutively active PIK3CA. In conclusion, YB-1 is the first reported oncogene to induce the expression of PIK3CA through transcriptional control of its promoter.

Authors+Show Affiliations

Laboratory for Oncogenomic Research, Departments of Pediatrics and Experimental Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19430491

Citation

Astanehe, A, et al. "The Transcriptional Induction of PIK3CA in Tumor Cells Is Dependent On the Oncoprotein Y-box Binding Protein-1." Oncogene, vol. 28, no. 25, 2009, pp. 2406-18.
Astanehe A, Finkbeiner MR, Hojabrpour P, et al. The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1. Oncogene. 2009;28(25):2406-18.
Astanehe, A., Finkbeiner, M. R., Hojabrpour, P., To, K., Fotovati, A., Shadeo, A., Stratford, A. L., Lam, W. L., Berquin, I. M., Duronio, V., & Dunn, S. E. (2009). The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1. Oncogene, 28(25), 2406-18. https://doi.org/10.1038/onc.2009.81
Astanehe A, et al. The Transcriptional Induction of PIK3CA in Tumor Cells Is Dependent On the Oncoprotein Y-box Binding Protein-1. Oncogene. 2009 Jun 25;28(25):2406-18. PubMed PMID: 19430491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1. AU - Astanehe,A, AU - Finkbeiner,M R, AU - Hojabrpour,P, AU - To,K, AU - Fotovati,A, AU - Shadeo,A, AU - Stratford,A L, AU - Lam,W L, AU - Berquin,I M, AU - Duronio,V, AU - Dunn,S E, Y1 - 2009/05/11/ PY - 2009/5/12/entrez PY - 2009/5/12/pubmed PY - 2009/7/16/medline SP - 2406 EP - 18 JF - Oncogene JO - Oncogene VL - 28 IS - 25 N2 - PIK3CA, which codes for the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), is implicated as an oncogene. Despite importance of PIK3CA in cancer, little is known about what drives up its expression in tumor cells. We recently characterized the PIK3CA promoter and reported that it is transcriptionally silenced by the tumor suppressor protein p53. In the present study, we demonstrate that PIK3CA can be induced by the oncogenic transcription factor Y-box binding protein-1 (YB-1). Three YB-1-responsive elements were identified on the PIK3CA promoter using chromatin immunoprecipitation and electrophoretic mobility shift assays. Interestingly, silencing YB-1 with siRNA in models of basal-like breast cancer decreased p110alpha protein levels regardless of whether PIK3CA was wild type, amplified or mutated. This decrease in p110alpha led to a reduction in PI3K activity and the downstream signaling primarily through p90 ribosomal S6 kinase and S6 ribosomal protein. Disruption in PIK3CA-dependent signaling suppressed cellular invasion correlative with loss of urokinase plasminogen activator (uPA). Similarly, silencing YB-1 suppressed invasion and uPA production however this was reversible through the introduction of constitutively active PIK3CA. In conclusion, YB-1 is the first reported oncogene to induce the expression of PIK3CA through transcriptional control of its promoter. SN - 1476-5594 UR - https://www.unboundmedicine.com/medline/citation/19430491/The_transcriptional_induction_of_PIK3CA_in_tumor_cells_is_dependent_on_the_oncoprotein_Y_box_binding_protein_1_ L2 - http://dx.doi.org/10.1038/onc.2009.81 DB - PRIME DP - Unbound Medicine ER -