Lead articleChanges in gene expression during progression of ovarian carcinoma
Introduction
The majority of ovarian malignancies arise from the surface epithelium. They are classified into several histological subtypes according to their cell type, serous, mucinous and endometrioid types being the most common. Tumors with serous histology comprise approximately 50% of the cases. The biological and clinical course of serous ovarian carcinoma is characterized by invasive behaviour, early dissemination to the peritoneal cavity, and poor prognosis [1].
Knowledge of the molecular genetic background of ovarian carcinoma is still scarce. The different histological subtypes of ovarian carcinoma share numerous genetic changes, and some alterations are specific for a certain histological subtype. Serous ovarian carcinoma exhibits frequent abnormal cytogenetic karyotypes, common DNA sequence copy number changes at chromosome 8 2, 3, 4, and molecular genetic changes in the ERBB2 and TP53 genes 5, 6. However, several other yet unidentified genes are most probably involved in the development and progression of serous ovarian carcinoma.
Gene expression studies provide means for finding the genes relevant for cancer development and progression. A new approach is a complementary DNA (cDNA) microarray technique, which allows simultaneous expression analysis of hundreds or even thousands of genes in the sample of interest. This large scale expression survey has been successfully applied to investigate gene expression profiling in different human cancers 7, 8, 9, 10.
We used cDNA array technique to carry out a large scale survey of differentially expressed genes that might be associated with the development and progression of serous ovarian adenoma to local and advanced adenocarcinoma.
Section snippets
Tissue samples
Tissue samples were obtained from seven patients treated at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital (Table 1). The study was approved by the Institutional Review Board. The samples were snap frozen in liquid nitrogen and stored at −70°C before RNA isolation. All ovarian tumors, including benign adenoma, exhibited serous histology (Table 1). The predominance of tumor cells (80–90%) in each carcinoma sample was microscopically verified.
RNA isolation
The frozen tissue
Ovarian adenocarcinoma versus benign adenoma
All six adenocarcinomas were compared with benign adenoma. Altogether 57 differentially expressed genes were detected in adenocarcinoma. Thirty-eight of these genes were upregulated and 19 were downregulated. Sixteen genes were upregulated and nine were downregulated in all carcinoma samples. The upregulated genes included Rho family genes (Ly-GDI, Rho8, Rho dissociation inhibitor 1), oncogenes and tumor suppressor genes (MET, MDM2s, STAT1, RBQ1), cell-cell interaction genes (Ne-dlg, cadherin
Discussion
The cDNA array analysis of serous ovarian carcinoma disclosed many genes with altered expression levels. Of particular interest are those which were differentially expressed in the majority of tumors, because frequent association may indicate a specific role in the development and progression of serous ovarian carcinoma. Some of the changes found in this study, e.g., overexpression of MET, AKT2 and PCNA 11, 12, 13, have been reported earlier in serous ovarian carcinoma. The present results thus
Acknowledgments
We thank Drs. P. Lehtovirta, A. Tenhunen and K. Ylinen for assistance in collecting the material. The technical assistance of Ms. A. Harju and Ms. R. Soitinaho are gratefully acknowledged. The study was supported by grants from the Helsinki University Hospital Research Funds, the Finnish Cancer Foundation, Finnish Medical Society, Finnish Cultural Foundation, and the Finnish Foundation for Obstetrics and Gynecology.
References (24)
- et al.
High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma
Am J Pathol
(1999) Rho guanine dissociation inhibitorspivotal molecules in cellular signalling
Cell Signal
(1999)- et al.
Specific contributions of the small GTPase Rho, Rac, and Cdc42 to Dbl transformation
J Biol Chem
(1999) - et al.
Activation of hepatocyte growth factor in the injured tissues is mediated by hepatocyte growth factor activator
J Biol Chem
(1996) - et al.
Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro
FEBS Lett
(1995) - et al.
Interferon-gamma regulates collagen and fibronectin gene expression by transcriptional and post-transcriptional mechanisms
Int J Biochem Cell Biol
(1997) - et al.
Genetic analysis of benign, low-grade, and high-grade ovarian tumors
Cancer Res
(1995) - et al.
Chromosome aberrations in 35 primary ovarian carcinomas
Genes Chromosomes Cancer
(1992) - et al.
Evidence for divergence of DNA copy number changes in serous, mucinous and endometrioid ovarian carcinomas
Br J Cancer
(1997)
Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer
Cancer Res
Overexpression and mutation of p53 in epithelial ovarian cancer
Cancer Res
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