FCCC LOGO Faculty Publications
Lian ZL , De Luca P , Di Cristofano A
Gene expression analysis reveals a signature of estrogen receptor activation upon loss of Pten in a mouse model of endometrial cancer
JOURNAL OF CELLULAR PHYSIOLOGY. 2006 Aug;208(2) :255-266
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Loss of PTEN is the earliest detectable genetic lesion in the endometrioid subtype of endometrial cancer (EEC), a tumor thought to be associated with an increase in unopposed estrogen activity. Pten(+)/(-) mice develop endometrial neoplastic lesions with full penetrance, despite having normal estrogen levels. We have utilized oligonucleoticle arrays to identify the alterations in gene expression patterns associated with loss of Pten and consequent neoplastic transformation of the endometrium. We show that 487 and 330 genes are substantially up- and downregulated, respectively, in Pten(+/-) mice. Several genes whose expression levels are impacted by loss of Pten are associated with pathways and functions that are relevant to the transformation and progression processes. Strikingly, we found that the expression levels of over 100 genes known to be regulated by estrogen receptor alpha (ER alpha) are also altered in the neoplastic uterus from Pten(+)/(-) mice, thus mimicking a h! yperestrogenic environment. These results provide in vivo evidence supporting the hypothesis that loss of Pten and subsequent Akt activation result in the activation of several ER alpha-dependent pathways that, mimicking increased estrogen signaling, may play a pivotal role in the neoplastic process.