PXD002797

PXD002797 is an original dataset announced via ProteomeXchange.

Title	Dynamics of protein expression reveals primary targets and secondary messengers of estrogen receptor signaling in MCF-7 breast cancer cells
Description	Estrogen receptor-mediated proliferation of breast cancer cells is facilitated through expression of multiple primary target genes, products of which induce the secondary response to stimulation. To differentiate between the primary and secondary target genes of estrogen receptor signaling, we measured dynamics of protein expression induced by estradiol in MCF-7 breast cancer cells. Measurement of the global proteomic effects of estradiol by SILAC resulted in identification of 104 estradiol-regulated proteins, with only 41 corresponding genes having estrogen response elements (EREs). Selected reaction monitoring assays were used to validate 32 proteins and measure the dynamics of their expression within 72 hours upon estradiol stimulation and in the presence of 4-hydroxytamoxifen, thus confirming estrogen receptor-mediated signaling. Dynamics of protein expression revealed immediate early response proteins including TFF1 and CDK1 and delayed response proteins including CDK2 and NAB2. Presence or absence of EREs in the corresponding genes indicated early or delayed expression of proteins identified by SILAC. Finally, we measured accurate dynamics of estradiol-induced protein expression in the sub-network of primary and secondary targets of estrogen receptor. Interestingly, since NAB2 protein is also a repressor of EGR3-induced transcription, siRNA-mediated silencing of NAB2 resulted in the over-expression of some EGR3-induced proteins, such as ITGA2. To conclude, quantitative proteomics revealed secondary targets of estrogen receptor signaling potentially overlooked by genome-wide profiling of EREs and provided dynamics of protein expression in the network of transcription factors with a negative feedback loop.
HostingRepository	PRIDE
AnnounceDate	2016-04-14
AnnouncementXML	Submission_2016-04-14_03:37:58.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrei Drabovich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C: 2x(15)N labeled L-lysine; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; 6x(13)C labeled L-arginine
Instrument	LTQ Orbitrap XL

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-26 02:44:25	ID requested
⏵ 1	2016-04-14 03:38:09	announced

Drabovich AP, Pavlou MP, Schiza C, Diamandis EP, Dynamics of Protein Expression Reveals Primary Targets and Secondary Messengers of Estrogen Receptor Alpha Signaling in MCF-7 Breast Cancer Cells. Mol Cell Proteomics, 15(6):2093-107(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: estrogen receptor, estradiol, ERE, estrogen-regulated proteins, SILAC, SRM, MCF-7

Andrei Drabovich
contact affiliation	Staff Scientist, Department of Clinical Biochemistry, University Health Network, Toronto, Canada Assistant Professor, Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada
contact email	andrei.drabovich@utoronto.ca
lab head
Andrei Drabovich
contact affiliation	University of Toronto
contact email	andrei.drabovich@utoronto.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002797
     1. Label: PRIDE project
     2. Name: Dynamics of protein expression reveals primary targets and secondary messengers of estrogen receptor signaling in MCF-7 breast cancer cells