A progesterone-induced endometrial homolog of a new candidate tumor suppressor, DMBT1.
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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Department of Obstetrics and Gynecology, University of Massachusetts Medical School, Worcester 01655, USA.
Okulicz
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WC
D000373:Agglutinins; D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004717:Endometrium / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
D000373:Agglutinins; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D011374:Progesterone