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Title: | Retinoic acid pathway genes show significantly altered expression in uterine fibroids when compared with normal myometrium. | Authors: | Vollenhoven B.J. ;Rogers P.A.W.;Zaitseva M. | Monash Health Department(s): | Obstetrics and Gynaecology (Monash Women's) | Institution: | (Zaitseva, Vollenhoven, Rogers) Centre for Women's Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Institute of Medical Research, Clayton, VIC, Australia (Vollenhoven) Women's and Children's Program, Southern Health, Melbourne, VIC, Australia | Issue Date: | 17-Oct-2012 | Copyright year: | 2007 | Publisher: | Oxford University Press (Great Clarendon Street, Oxford OX2 6DP, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Molecular Human Reproduction. 13 (8) (pp 577-585), 2007. Date of Publication: August 2007. | Abstract: | Fibroids are benign neoplasms of myometrial smooth muscle cells (SMC). Despite being the most common tumor in humans, their etiology is poorly understood. Recent microarray studies have demonstrated that multiple members of the retinoid pathway are differentially expressed between myometrium and fibroids. The aim of this present study was to investigate gene expression of members of the retinoid pathway in matched myometrium and fibroids. We have demonstrated differential gene expression of two binding proteins [cellular retinol-binding proteins (CRBP) 1 and 2], three enzymes [alcohol dehydrogenase 1 (ADH1), aldehyde dehydrogenase (ALDH1) and retinol dehydrogenase (RODH)] and two receptors [retinoid X receptors (RXR) alpha and gamma] involved in the retinoid pathway by real-time PCR. There were no differences in gene expression for retinoid receptors RARalpha, beta, gamma and RXRbeta, and for the metabolizing enzyme cytochrome P450, family 26 subfamily A. We confirmed results for ADH1, ALDH1, CRBP1 and CRABP2 at the protein level by western blot. Using immunohistochemistry these proteins were mostly localized to myometrial and fibroid SMC. An exception to this was ALDH1 protein, which displayed strong staining localized to cells of the connective tissue, presumably fibroblasts, with a striking differential expression pattern between myometrium and fibroids. These results demonstrate that the retinoid pathway is altered in fibroids when compared with normal myometrium and specifically identify ALDH1 in fibroid fibroblasts. These alterations can lead to aberrant retinoic acid (RA) production and signaling, and alter the expression of RA target genes, which may be an important step in fibroid development. © The Author 2007. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1093/molehr/gam040 | PubMed URL: | 17553814 [http://www.ncbi.nlm.nih.gov/pubmed/?term=17553814] | ISSN: | 1360-9947 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/31794 | Type: | Article | Subjects: | real time polymerase chain reaction smooth muscle fiber *uterus myoma/et [Etiology] *uterus myoma/su [Surgery] Western blotting *alcohol dehydrogenase/ec [Endogenous Compound] *aldehyde dehydrogenase/ec [Endogenous Compound] *cellular retinol binding protein 1/ec [Endogenous Compound] cytochrome P450/ec [Endogenous Compound] *retinoic acid/ec [Endogenous Compound] retinoid *retinoid X receptor alpha/ec [Endogenous Compound] retinoid X receptor gamma/ec [Endogenous Compound] retinol dehydrogenase/ec [Endogenous Compound] signal transduction adult article benign tumor clinical article connective tissue controlled study female fibroblast gene expression human human tissue immunohistochemistry myometrium priority journal protein localization immunohistochemistry myometrium priority journal protein localization real time polymerase chain reaction signal transduction smooth muscle fiber *uterus myoma / *etiology / *surgery benign tumor article adult Western blotting clinical article connective tissue controlled study female fibroblast gene expression human human tissue |
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