Показать сокращенную информацию
dc.contributor.author | Zhang Y. | |
dc.contributor.author | Nasto R. | |
dc.contributor.author | Varghese R. | |
dc.contributor.author | Jablonski S. | |
dc.contributor.author | Serebriiskii I. | |
dc.contributor.author | Surana R. | |
dc.contributor.author | Calvert V. | |
dc.contributor.author | Bebu I. | |
dc.contributor.author | Murray J. | |
dc.contributor.author | Jin L. | |
dc.contributor.author | Johnson M. | |
dc.contributor.author | Riggins R. | |
dc.contributor.author | Ressom H. | |
dc.contributor.author | Petricoin E. | |
dc.contributor.author | Clarke R. | |
dc.contributor.author | Golemis E. | |
dc.contributor.author | Weiner L. | |
dc.date.accessioned | 2018-09-19T20:42:01Z | |
dc.date.available | 2018-09-19T20:42:01Z | |
dc.date.issued | 2016 | |
dc.identifier.issn | 0950-9232 | |
dc.identifier.uri | https://dspace.kpfu.ru/xmlui/handle/net/143150 | |
dc.description.abstract | © 2016 Macmillan Publishers Limited.Resistance to therapies targeting the estrogen pathway remains a challenge in the treatment of estrogen receptor-positive breast cancer. To address this challenge, a systems biology approach was used. A library of small interfering RNAs targeting an estrogen receptor (ER)-and aromatase-centered network identified 46 genes that are dispensable in estrogen-dependent MCF7 cells, but are selectively required for the survival of estrogen-independent MCF7-derived cells and multiple additional estrogen-independent breast cancer cell lines. Integration of this information identified a tumor suppressor gene TOB1 as a critical determinant of estrogen-independent ER-positive breast cell survival. Depletion of TOB1 selectively promoted G1 phase arrest and sensitivity to AKT and mammalian target of rapmycin (mTOR) inhibitors in estrogen-independent cells but not in estrogen-dependent cells. Phosphoproteomic profiles from reverse-phase protein array analysis supported by mRNA profiling identified a significant signaling network reprogramming by TOB1 that differed in estrogen-sensitive and estrogen-resistant cell lines. These data support a novel function for TOB1 in mediating survival of estrogen-independent breast cancers. These studies also provide evidence for combining TOB1 inhibition and AKT/mTOR inhibition as a therapeutic strategy, with potential translational significance for the management of patients with ER-positive breast cancers. | |
dc.relation.ispartofseries | Oncogene | |
dc.title | Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation | |
dc.type | Article | |
dc.relation.ispartofseries-issue | 13 | |
dc.relation.ispartofseries-volume | 35 | |
dc.collection | Публикации сотрудников КФУ | |
dc.relation.startpage | 1643 | |
dc.source.id | SCOPUS09509232-2016-35-13-SID84949965535 |