A progesterone-induced endometrial homolog of a new candidate tumor suppressor, DMBT1
Ace, Christopher I. ; Okulicz, William C.
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Student Authors
Faculty Advisor
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UMass Chan Affiliations
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Keywords
Amino Acid Sequence
Animals
Endometrium
Female
Gene Expression
Genes, Tumor Suppressor
Humans
In Situ Hybridization
Macaca mulatta
Molecular Sequence Data
Polymerase Chain Reaction
Progesterone
Receptors, Cell Surface
Sequence Homology, Amino Acid
Life Sciences
Medicine and Health Sciences
Subject Area
Embargo Expiration Date
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Abstract
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.
Source
J Clin Endocrinol Metab. 1998 Oct;83(10):3569-73.