Transcriptional profiling endometrial carcinomas microdissected from DES-treated mice identifies changes in gene expression associated with estrogenic tumor promotion

Omar Kabbarah, Mary Ann Mallon, John P. Pfeifer, Paul J. Goodfellow

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Exposure to unopposed estrogen is a potent risk factor for developing human endometrial cancer. However, little is known about the transcriptional changes elicited by estrogens in endometrial carcinogenesis, in part, because of genetic and environmental heterogeneity of human tumors. We have begun to chart the expression signatures of endometrial tumors promoted with the synthetic estrogen, diethylstilbestrol (DES), in inbred mice. As expected, laser-capturemicrodissected endometrial cancers from DES-treated mice displayed a large number of transcriptional changes when compared to uninvolved endometrial epithelium. Genes differentially expressed in carcinomas included cell adhesion and extracellular matrix genes (Decorin as 1 example), developmental genes (Hoxall), and cytokine signaling genes (Socs3). The DES-promoted carcinomas appeared to fall into 2 distinct transcriptional classes, and expression of the tumor suppressor Pten was among the top discriminators between the 2 cancer groups. Pten was down regulated in the majority of the DES-promoted carcinomas, which is analogous to the frequent loss of PTEN expression in human endometrial tumors. Although preliminary, these observations suggest that the cancers that arise in the DES model bear similarities to human endometrial cancers and provide insights into transcriptional alterations that accompany estrogen-driven endometrial carcinogenesis.

Original languageEnglish
Pages (from-to)1843-1849
Number of pages7
JournalInternational Journal of Cancer
Volume119
Issue number8
DOIs
StatePublished - Oct 15 2006

Keywords

  • DES
  • Endometrial carcinoma
  • Gene expression profiling
  • Mouse model

Fingerprint Dive into the research topics of 'Transcriptional profiling endometrial carcinomas microdissected from DES-treated mice identifies changes in gene expression associated with estrogenic tumor promotion'. Together they form a unique fingerprint.

  • Cite this