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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Signal pathway profiling of ovarian cancer from human tissue specimens using reverse-phase protein microarrays
Julia D Wulfkuhle1, Joy A Aquino, Valerie S Calvert
1Center for Cancer Research, National Cancer Institute/NIH, Building 29A/Room 2B20, 8000 Rockville Pike, Bethesda, MD 20892, USA. wulfkuhle@cber.fda.gov
Abstract:
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.
Insights
Ovarian cancer signaling pathways show significant patient-specific activation patterns. Proteomics reveals that key survival and proliferation signals vary within tumor types, suggesting personalized treatment approaches for cancer.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Cell signaling pathway defects are crucial in cancer progression, including growth, survival, invasion, and metastasis.
- Understanding these pathways is vital for developing targeted cancer therapies.
- Proteomics aims to map these signaling circuits in normal and diseased cells.
Purpose of the Study:
- To characterize signaling pathway activation in human ovarian tumors using advanced proteomics.
- To investigate the role of key proteins like ERK1/2 and Akt in ovarian cancer.
- To determine if pathway activation patterns differ between ovarian tumor histotypes or stages.
Main Methods:
- Utilized reverse-phase protein array technology.
- Employed laser capture microdissection to isolate specific cell populations.
- Used phospho-specific antibodies to analyze the activation status of signaling proteins.
Main Results:
- Extracellular-regulated kinase (ERK1/2) activation varied within histotypes but not significantly between them.
- Advanced stage ovarian tumors showed slightly higher phosphorylated ERK1/2 levels than early stage tumors.
- Phosphatidylinositol 3-kinase/Akt pathway proteins (Akt, GSK3beta) exhibited more variation within histotypes than between them.
Conclusions:
- Reverse phase protein microarrays are effective for analyzing signal transduction in human tumor tissues.
- Ovarian tumor signaling pathway activation patterns appear to be patient-specific rather than histotype or stage-specific.
- Findings suggest potential for personalized therapeutic strategies based on individual tumor signaling profiles.
