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Open Access Highly Accessed Research article

Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells

Nathan J Bowen123, L DeEtte Walker123, Lilya V Matyunina123, Sanjay Logani4, Kimberly A Totten123, Benedict B Benigno3 and John F McDonald123*

Author Affiliations

1 School of Biology, Georgia Institute of Technology, Atlanta, GA, USA

2 Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA

3 Ovarian Cancer Institute, Atlanta, GA, USA

4 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

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BMC Medical Genomics 2009, 2:71  doi:10.1186/1755-8794-2-71

Published: 29 December 2009

Abstract

Background

Accumulating evidence suggests that somatic stem cells undergo mutagenic transformation into cancer initiating cells. The serous subtype of ovarian adenocarcinoma in humans has been hypothesized to arise from at least two possible classes of progenitor cells: the ovarian surface epithelia (OSE) and/or an as yet undefined class of progenitor cells residing in the distal end of the fallopian tube.

Methods

Comparative gene expression profiling analyses were carried out on OSE removed from the surface of normal human ovaries and ovarian cancer epithelial cells (CEPI) isolated by laser capture micro-dissection (LCM) from human serous papillary ovarian adenocarcinomas. The results of the gene expression analyses were randomly confirmed in paraffin embedded tissues from ovarian adenocarcinoma of serous subtype and non-neoplastic ovarian tissues using immunohistochemistry. Differentially expressed genes were analyzed using gene ontology, molecular pathway, and gene set enrichment analysis algorithms.

Results

Consistent with multipotent capacity, genes in pathways previously associated with adult stem cell maintenance are highly expressed in ovarian surface epithelia and are not expressed or expressed at very low levels in serous ovarian adenocarcinoma. Among the over 2000 genes that are significantly differentially expressed, a number of pathways and novel pathway interactions are identified that may contribute to ovarian adenocarcinoma development.

Conclusions

Our results are consistent with the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as the origin of ovarian adenocarcinoma. While our findings do not rule out the possibility that ovarian cancers may also arise from other sources, they are inconsistent with claims that ovarian surface epithelia cannot serve as the origin of ovarian cancer initiating cells.