Characterization of the homeodomain gene EMX2: sequence conservation, expression analysis, and a search for mutations in endometrial cancers.

Previous loss-of-heterozygosity studies in endometrial carcinoma mapped a putative tumor suppressor gene to 10q25.3-26.1. An analysis of genomic sequences for the deletion interval showed several expressed sequence tags and the homeodomain gene EMX2, a homologue of Drosophila melanogaster empty spiracles. Expression studies showed that EMX2 transcripts are abundant in the adult uterus and that message levels seem to be inversely correlated with endometrial proliferation. EMX2 RNA was more abundant in quiescent postmenopausal endometrium than in premenopausal endometrium. We found decreased EMX2 expression in a subset of primary endometrial tumors, and four of six endometrial cancer cell lines investigated failed to express EMX2. The predicted protein showed extensive amino acid conservation with EMX2 sequences from several vertebrates. There was also considerable evolutionary conservation in the 3' untranslated region. To examine the potential function of EMX2 in endometrial tumorigenesis, we investigated 20 primary tumors and 6 endometrial cancer cell lines for mutations. Two primary tumors had mutations. Inactivation or reduced expression of EMX2 in cancers, coupled with increased expression in the quiescent endometrium, indicate that this homeodomain gene is involved in maintenance of the differentiated state.