Dataset Information

Comparative Membrane Proteomics Analyses of Breast Cancer Cell Lines to Understand the Molecular Mechanism of Breast Cancer Brain Metastasis

ABSTRACT: Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is considered as an essential issue in breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis that contributes to the cell adhesion and penetration of blood-brain barrier. To achieve a deeper insight of the mechanism of breast cancer brain metastasis, liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed to analyze the enriched membrane proteomes from six different breast cancer cell lines. Quantitative proteomic data of all cell lines were compared with MDA-MB-231BR which has the specific brain metastasis capacity. 1239 proteins were identified and 990 were quantified with more than 70% of membrane proteins in all cell lines. Each cell line can be separated apart from others in PCA. Ingenuity pathway analysis (IPA) supported the high brain metastatic ability of 231BR and suggested importance of the up-regulation of integrin proteins and down-regulation of EPHA in brain metastasis. 28 proteins were observed unique expression alteration in 231BR. The up-regulation of NPM1, hnRNP Q, hnRNP K and eIF3l and the down-regulation of TUBB4B and TUBB were observed to be associated with the brain metastasis cell line and may contributes to the breast cancer brain metastasis.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Wenjing Peng

LAB HEAD: Yehia Mechref

PROVIDER: PXD005719 | Pride | 2017-05-23

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 36

Publications

Comparative membrane proteomics analyses of breast cancer cell lines to understand the molecular mechanism of breast cancer brain metastasis.

Peng Wenjing W Zhang Yu Y Zhu Rui R Mechref Yehia Y

Electrophoresis 20170705 17

Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the pr ...[more]

PMID: 28523741

Similar Datasets

Project description:Introduction: The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, calcium-activated potassium (BK) channel is significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene, which encodes α subunit of KCa channels (BK channels) in breast cancer metastasis and invasion. Methods: We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer in brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of α subunit of KCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether KCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with IBTX (Iberiotoxin). Results: The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BK channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion: Determining the relative abundance of BK channel over expression in breast cancer metastatic to brain and the mechanism of its action in brain metastasis will provide a unique opportunity to identify and differentiate between low grade breast tumors that are at high risk for metastasis from those at low risk for metastasis. This distinction would in turn allow for the appropriate and efficient application of effective treatments while sparing patients with low risk for metastasis from the toxic side effects of chemotherapy.

			Action	DRS
	F008035.dat	Other
	F008036.dat	Other
	F008037.dat	Other
	F008038.dat	Other
	F008039.dat	Other