Protein Kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs).

Abstract

KIT expression is a key diagnostic feature of gastrointestinal stromal tumors (GISTs), and virtually all of the GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as therapeutic targets of imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdiagnosis as other types of sarcoma. We report that the signaling intermediate protein kinase C theta (PKCtheta) is a diagnostic marker in GISTs, including those that lack KIT expression and/or contain PDGFRA mutations. PKCtheta is strongly activated in most GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.

• Authors: Anette Duensing, Nora E Joseph, Fabiola Medeiros, Felicity Smith, Jason L Hornick, Michael C Heinrich, Christopher L Corless, George D Demetri, Christopher D M Fletcher, Jonathan A Fletcher
• Journal: Cancer research (Cancer Res) Vol. 64 Issue 15 Pg. 5127-31 (Aug 01 2004) ISSN: 0008-5472 [Print] United States
• PMID: 15289315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Oncogene Proteins
• Proto-Oncogene Proteins c-kit
• Receptor, Platelet-Derived Growth Factor alpha
• PRKCQ protein, human
• Protein Kinase C
• Protein Kinase C-theta

Topics

• Enzyme Activation
• Gastrointestinal Neoplasms (metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Immunoenzyme Techniques
• Isoenzymes (metabolism)
• Mutation
• Oncogene Proteins (genetics, metabolism)
• Phosphorylation
• Protein Kinase C (metabolism)
• Protein Kinase C-theta
• Proto-Oncogene Proteins c-kit
• Receptor, Platelet-Derived Growth Factor alpha (genetics, metabolism)
• Stromal Cells (metabolism, pathology)
• Zinc Fingers