The Mammary Epithelial Cell Secretome and its Regulation by Signal Transduction Pathways
Extracellular proteins released by mammary epithelial cells are critical mediators of cell communication, proliferation and organization, yet the actual spectrum of proteins released by any given cell (the secretome) is poorly characterized. To define the set of proteins secreted by human mammary epithelial cells (HMEC), we combined analytical and computational approaches to define a secretome protein set based upon probable biological significance. Analysis of HMEC-conditioned medium by liquid chromatography-mass spectrometry resulted in identification of 889 unique proteins, of which 151 were found to be specifically enriched in the extracellular compartment when compared with a database of proteins expressed in whole HMEC lysates. Additional high mass accuracy analysis revealed 36 proteins whose extracellular abundance increased after treatment with phorbol ester (PMA), a protein kinase C agonist and general secretagogue. Many of the PMA stimulated proteins have been reported to be aberrantly expressed in human cancers and appear to be co-regulated as multigene clusters. By inhibiting PMA-mediated transactivation of the epidermal growth factor receptor (EGFR), a pathway critically required for normal HMEC function, we found that the secretion of specific matrix metalloproteases were also coordinately regulated through EGFR transactivation. This study demonstrates a tiered strategy by which extracellular proteins can be identified and progressively assigned to classes of increasing confidence and regulatory importance.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 923674
- Report Number(s):
- PNNL-SA-56310; TRN: US200804%%1385
- Journal Information:
- Journal of Proteome Research, 7(2):558-569, Vol. 7, Issue 2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL PROTECTION
ABUNDANCE
ACCURACY
COMPARTMENTS
GROWTH FACTORS
PHORBOL ESTERS
PHOSPHOTRANSFERASES
PROLIFERATION
PROTEINS
REGULATIONS
SECRETION
SPECTROSCOPY
proteome of secreted proteins
mammary epithelial cell
phorbol ester
epidermal growth factor receptor
mass spectrometry