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 |
|