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Signal pathway profiling of prostate cancer using reverse phase protein arrays
Author(s) -
Grubb Robert L.,
Calvert Valerie S.,
Wulkuhle Julia D.,
Paweletz Cloud P.,
Linehan W. Marston,
Phillips John L.,
Chuaqui Rodrigo,
Valasco Alfredo,
Gillespie John,
EmmertBuck Michael,
Liotta Lance A.,
Petricoin Emanuel F.
Publication year - 2003
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200300598
Subject(s) - laser capture microdissection , biology , prostate cancer , signal transduction , proteomics , protein microarray , carcinogenesis , cancer research , prostate , cell signaling , tissue microarray , tumor progression , cancer , microbiology and biotechnology , microarray , gene expression , genetics , gene
Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro‐survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho‐specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient‐tailored therapy.