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A Progesterone-Induced Endometrial Homolog of a New Candidate Tumor Suppressor, DMBT1¹

Departments of Obstetrics and Gynecology and Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655

Address all correspondence and requests for reprints to: William C. Okulicz, Ph.D., Department of Obstetrics and Gynecology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655. E-mail: william.okulicz{at}banyan.ummed.edu

We have previously prepared and characterized a subtracted library enriched for endometrial progesterone (P)-dependent genes in the rhesus monkey. One of the fragment clones (H3) that we selected for sequencing from this library was found to be homologous to human DMBT1, a recently isolated member of the scavenger receptor cysteine-rich superfamily and a new putative tumor suppressor. In this report, we provide evidence that H3 is the rhesus monkey homolog of DMBT1. Additional sequence data of H3 (1071 bp) showed a striking homology with DMBT1 (92% identical). Semiquantitative kinetic PCR of estrogen-dominant vs. P-dominant endometrial complementary DNA populations showed that the H3 gene was up-regulated 5-fold by normal secretory P levels. In situ hybridization with unique probes to H3 confirmed the up-regulation by P in the endometrium and a restricted expression in the stromal compartment. Another recent report suggested the presence of an endometrial tumor suppressor in the same chromosomal region as DMBT1 (10q23–26); deletions in this region were associated with endometrial cancers. Together, these studies potentially provide a molecular link to the protective effect of the action of P on unopposed estrogen exposure in reproductive tract cancers in women.

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