Use of Reverse Phase Protein Microarrays and Reference Standard Development for Molecular Network Analysis of Metastatic Ovarian Carcinoma

• Published in: Molecular & cellular proteomics Vol. 4; no. 4; pp. 346 - 355
• Main Authors: Sheehan, Katherine M, Calvert, Valerie S, Kay, Elaine W, Lu, Yiling, Fishman, David, Espina, Virginia, Aquino, Joy, Speer, Runa, Araujo, Robyn, Mills, Gordon B, Liotta, Lance A, Petricoin, 3rd, Emanuel F, Wulfkuhle, Julia D
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 01-04-2005
• Subjects: Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - pathology; Female; Humans; Molecular Biology - methods; Neoplasm Metastasis - pathology; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Peptides - chemistry; Peptides - metabolism; Phosphorylation; Protein Array Analysis - methods; Proteomics - methods; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Signal Transduction
• ISSN: 1535-9476; 1535-9484; 1535-9484
• DOI: 10.1074/mcp.T500003-MCP200

Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling
events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways,
providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian
epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected
until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions
are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic
microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation
end points may require evaluation of the patient’s metastatic tissue. Extending these findings to the bedside will require
the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture
of phosphorylated peptides to begin to address this challenge.