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Differential Gene Expression in Ovarian Tumors Reveals Dusp 4 and Serpina 5 As Key Regulators for Benign Behavior of Serous Borderline Tumors
- Source :
- Journal of Clinical Oncology. 23:7257-7264
- Publication Year :
- 2005
- Publisher :
- American Society of Clinical Oncology (ASCO), 2005.
-
Abstract
- Purpose Ovarian serous borderline tumors (SBT) are characterized by arborizing papillae lined by stratified epithelial cells, varying atypia, and absence of stromal invasion. Originally, these tumors have been classified as borderline because they behaved in a remarkably indolent manner, even with widespread tumor deposits called implants and the presence of lymph node involvement. The molecular biology of these lesions has just begun to be explored. High prevalence of B-RAF/K-RAS mutations in SBTs in contrast to serous carcinomas (SCAs) indicates that the mitogenic RAS-RAF-MEK-ERK-MAP kinase pathway is crucial for the pathogenesis of SBTs. The purpose of this study was to further unravel the genetic pathways through which SBTs develop, with a special focus on explaining the generally benign SBT behavior. Materials and Methods We generated RNA expression profiles of 38 ovarian serous neoplasms. Global Test pathway analysis and significance analysis of microarrays (SAM) of the expression profiles was performed. Results SAM and Global Testing showed that although the mitogenic pathway is activated in SBTs, activation of downstream genes involved in extracellular matrix (ECM) degradation is absent, suggesting an uncoupling of both events. In addition, we show that two genes involved in regulating this uncoupling, ERK-inhibitor Dusp 4 and uPA-inhibitor Serpina 5, are downregulated in SCAs in contrast to SBTs. In SCAs, this was associated with downstream MMP-9 activation at both mRNA and protein level. Conclusion We propose that the putative tumor suppressor genes Dusp 4 and Serpina 5 provide a major clue to the indolent behavior of SBTs.
- Subjects :
- Proto-Oncogene Proteins B-raf
Cancer Research
Pathology
medicine.medical_specialty
Gene Expression
Biology
medicine.disease_cause
Stromal Invasion
Ovarian tumor
Atypia
medicine
Humans
Genes, Tumor Suppressor
Lymph node
Oligonucleotide Array Sequence Analysis
Protein C Inhibitor
Ovarian Neoplasms
Gene Expression Profiling
Cancer
medicine.disease
Gene expression profiling
Serous fluid
Genes, ras
medicine.anatomical_structure
Matrix Metalloproteinase 9
Oncology
Mutation
Dual-Specificity Phosphatases
Mitogen-Activated Protein Kinase Phosphatases
Female
KRAS
Protein Tyrosine Phosphatases
Neoplasms, Cystic, Mucinous, and Serous
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....b32bbf1ffd2d3eaf42822bb1e2bbfa48