Defects in cell signaling pathways play a central role in
cancer cell growth, survival, invasion and
metastasis. An important goal of proteomics is to characterize and develop "circuit maps" of these signaling pathways in normal and diseased cells. We have used reverse-phase
protein array technology coupled with
laser capture microdissection and
phospho-specific antibodies to examine the activation status of several key molecular "gates" involved in cell survival and proliferation signaling in human ovarian
tumor tissue. The levels of activated extracellular-regulated
kinase (ERK1/2) varied considerably in
tumors of the same histotype, but no significant differences between histotypes were observed. Advanced stage
tumors had slightly higher levels of phosphorylated ERK1/2 compared to early stage
tumors. The activation status of Akt and
glycogen synthase kinase 3beta, key
proteins and indicators of the state of the
phosphatidylinositol 3-kinase/Akt pro-survival pathway also showed more variation within each histotype than between the histotypes studied. Our results demonstrate the utility of reverse phase
protein microarrays for the multiplexed analysis of signal transduction from discreet cell populations of cells procured directly from human ovarian
tumor specimens and suggest that patterns in signal pathway activation in ovarian
tumors may be patient-specific rather than type or stage specific.