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Here we evaluate the effect of PI3K inhibition on global gene expression in breast cancer cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used a range of methodologies that include\n                      <jats:italic>in silico<\/jats:italic>\n                      compound analysis,\n                      <jats:italic>in vitro<\/jats:italic>\n                      kinase assays, cell invasion assays, proliferation assays, genome-wide transcription studies (Agilent Technologies full genome arrays), gene set enrichment analysis, quantitative real-time PCR, immunoblotting in addition to chromatin immunoprecipitation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We defined the physico-chemical and the biological properties of ETP-45658, a novel potent PI3K inhibitor. We demonstrated that ETP-45658 potently inhibited cell proliferation within a broad range of human cancer cells, most potently suppressing the growth of breast cancer cells via inhibiting cell cycle. We show that this response is Forkhead box O (FOXO) protein dependent and p53 independent. Our genome-wide microarray analysis revealed that the cell cycle was the most affected biological process after exposure to ETP-45658 (or our control PI3K inhibitor PI-103), that despite the multiple transcription factors that are regulated by the PI3K\/AKT signalling cascade, only the binding sites for FOXO transcription factors were significantly enriched and only a subset of all FOXO-dependent genes were induced. This disparity in gene transcription was not due to differential FOXO promoter recruitment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The constitutive activation of PI3Ks and thus the exclusion of FOXO transcription factors from the nucleus is a key feature of breast cancer. Our results presented here highlight that PI3K inhibition activates specific FOXO-dependent genes that mediate cell cycle arrest in breast cancer cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13058-014-0482-y","type":"journal-article","created":{"date-parts":[[2014,12,8]],"date-time":"2014-12-08T07:02:27Z","timestamp":1418022147000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["A novel phosphatidylinositol 3-kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regulated genes"],"prefix":"10.1186","volume":"16","author":[{"given":"Richard","family":"Hill","sequence":"first","affiliation":[]},{"given":"Ravi Kiran Reddy","family":"Kalathur","sequence":"additional","affiliation":[]},{"given":"Sergio","family":"Callejas","sequence":"additional","affiliation":[]},{"given":"Laura","family":"Cola\u00e7o","sequence":"additional","affiliation":[]},{"given":"Ricardo","family":"Brand\u00e3o","sequence":"additional","affiliation":[]},{"given":"Beatriz","family":"Serelde","sequence":"additional","affiliation":[]},{"given":"Antonio","family":"Cebri\u00e1","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Blanco-Aparicio","sequence":"additional","affiliation":[]},{"given":"Joaqu\u00edn","family":"Pastor","sequence":"additional","affiliation":[]},{"given":"Matthias","family":"Futschik","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Dopazo","sequence":"additional","affiliation":[]},{"given":"Wolfgang","family":"Link","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2014,12,9]]},"reference":[{"key":"482_CR1","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1002\/ijc.25516","volume":"127","author":"J Ferlay","year":"2010","unstructured":"Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. 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