Dataset Information

24hrs IGF-1 - Temporal proteomic analysis of IGF-1R signalling in MCF-7 breast adenocarcinoma cells

ABSTRACT: 24 hr stimulated MCF-7 cells (0,6,12,24 h) labelled with iTRAQ reagents

INSTRUMENT(S): QToF Global

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Patrick Murphy

LAB HEAD: Patrick Murphy

PROVIDER: PRD000178 | Pride | 2010-04-29

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	PRIDE_Exp_Complete_Ac_10639.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_10639.pride.mztab.gz	Mztab
	PRIDE_Exp_Complete_Ac_10639.xml.gz	Xml
	PRIDE_Exp_Complete_Ac_10885.pride.mgf.gz	Mgf
	PRIDE_Exp_Complete_Ac_10885.pride.mztab.gz	Mztab

Items per page:

1 - 5 of 12

Publications

Temporal proteomic analysis of IGF-1R signalling in MCF-7 breast adenocarcinoma cells.

Murphy J Patrick JP Pinto Devanand M DM

Proteomics 20100501 9

Dysregulation of the insulin-like growth factor 1 receptor signalling network is implicated in tumour growth and resistance to chemotherapy. We explored proteomic changes resulting from insulin-like growth factor 1 stimulation of MCF-7 adenocarcinoma cells as a function of time. Quantitative analysis using iTRAQ reagents and 2-D LC-MS/MS analysis of three biological replicates resulted in the identification of 899 proteins (p<or=0.05) with an estimated mean false-positive rate of 2.6%. Quantitat ...[more]

PMID: 20213678

Similar Datasets

Project description:Primary bone tumor, also known as osteosarcoma (OS), is the most common primary malignancy of bone in children and young adults. Current treatment protocols yield a 5-year survival rate of near 70% although approximately 80% of patients have metastatic disease at the time of diagnosis. However, long-term survival rates have remained virtually unchanged for nearly four decades, largely due to our limited understanding of the disease process. One major signaling pathway that has been implicated in human OS tumorigenesis is the insulin-like growth factor (IGF)/insulin-like growth factor-1 receptor (IGF1R) signaling axis. IGF1R is a heterotetrameric α2β2 receptor, in which the α subunits comprise the ligand binding site, whereas the β subunits are transmembrane proteins containing intracellular tyrosine kinase domains. Although numerous strategies have been devised to target IGF/IGF1R axis, most of them have failed in clinical trials due to the lack of specificity and/or limited efficacy. Here, we investigated whether a more effective and specific blockade of IGF1R activity in human OS cells can be accomplished by employing dominant-negative IGF1R (dnIGF1R) mutants. We engineered the recombinant adenoviruses expressing two IGF1R mutants derived from the α (aa 1-524) and β (aa 741-936) subunits, and found that either dnIGF1Rα and/or dnIGF1Rβ effectively inhibited cell migration, colony formation, and cell cycle progression of human OS cells, which could be reversed by exogenous IGF1. Furthermore, dnIGF1Rα and/or dnIGF1Rβ inhibited OS xenograft tumor growth in vivo, with the greatest inhibition of tumor growth shown by dnIGF1Rα. Mechanistically, the dnIGF1R mutants down-regulated the expression of PI3K/AKT and RAS/RAF/MAPK, BCL2, Cyclin D1 and most EMT regulators, while up-regulating pro-apoptotic genes in human OS cells. Collectively, these findings strongly suggest that the dnIGF1R mutants, especially dnIGF1Rα, may be further developed as novel anticancer agents that target IGF signaling axis with high specificity and efficacy.