Suppression of estrogen-dependent MMP-9 expression by Edpm5, a genetic locus for pituitary tumor growth in rat.
Chronic estrogen treatment results in elevated levels of the gelatinase pro-MMP-9 in the pituitary of tumor-susceptible Fischer 344 rats. In contrast, pituitary pro-MMP-9 level is not increased by estrogen treatment in rats of the tumor-resistant BN strain nor in rats of an F(1) hybrid of these strains. The gelatinase MMP-2 is also detected in rat pituitary, but its level is not affected by either estrogen or rat genotype. In 124 estrogen-treated rats from a backcross of the F(1) hybrid to the F344 strain, the levels of both monomer and dimer forms of pro-MMP-9 correlate with the tumor phenotypes mass, total DNA, and hemoglobin content of the pituitary. In this backcross, the QTL Edpm5 (_e_strogen-_d_ependent _p_ituitary _m_ass on Chromosome 5) has a significant effect on MMP-9 levels, with inheritance of the BN allele of Edpm5 correlating with suppression of estrogen-dependent MMP-9 expression.
Sclafani
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RV
Department of Biological Sciences, Oakland University, 2200 N. Squirrel Rd., Rochester, MI 48309-4401, USA.
Wendell
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DL
D000483:Alleles; D000818:Animals; D002455:Cell Division; D002874:Chromosome Mapping; D004054:Diethylstilbestrol / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D009928:Organ Specificity; D010911:Pituitary Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D019655:Quantitative Trait, Heritable; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D014599:Uterus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D004968:Estrogens, Non-Steroidal; D005819:Genetic Markers; D004054:Diethylstilbestrol; D020780:Matrix Metalloproteinase 9