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Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies.

ABSTRACT: INTRODUCTION:The stroma is the supportive framework of biologic tissue in the breast, consisting of various proteins such as the proteoglycans, decorin and lumican. Altered expression of decorin and lumican is associated with breast tumors. We hypothesized that genetic variation in the decorin (DCN) and lumican (LUM) genes may contribute to breast cancer. METHODS:We investigated associations of 14 common polymorphisms in the DCN and LUM genes with 798 breast cancer cases and 843 controls from Mayo Clinic, MN, USA. One polymorphism per gene with the strongest risk association in the Mayo Clinic sample was genotyped in 4,470 breast cancer cases and 4,560 controls from East Anglia, England (Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH)). RESULTS:In the Mayo Clinic sample, six polymorphisms were associated with breast cancer risk (P trend

SUBMITTER: Kelemen LE

PROVIDER: S-EPMC2656894 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies.

Kelemen Linda E LE Couch Fergus J FJ Ahmed Shahana S Dunning Alison M AM Pharoah Paul D P PD Easton Douglas F DF Fredericksen Zachary S ZS Vierkant Robert A RA Pankratz V Shane VS Goode Ellen L EL Scott Christopher G CG Rider David N DN Wang Xianshu X Cerhan James R JR Vachon Celine M CM

Breast cancer research : BCR 20081126 6

<h4>Introduction</h4>The stroma is the supportive framework of biologic tissue in the breast, consisting of various proteins such as the proteoglycans, decorin and lumican. Altered expression of decorin and lumican is associated with breast tumors. We hypothesized that genetic variation in the decorin (DCN) and lumican (LUM) genes may contribute to breast cancer.<h4>Methods</h4>We investigated associations of 14 common polymorphisms in the DCN and LUM genes with 798 breast cancer cases and 843 c ...[more]

PMID: 19036156

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Project description:Background and aimDuring prostate development, mesenchymal-epithelial interactions regulate organ growth and differentiation. In adult prostate, stromal-epithelial interactions are important for tissue homeostasis and also play a significant role in prostate cancer. In this study we have identified molecules that show a mesenchymal expression pattern in the developing prostate, and one of these showed reduced expression in prostate cancer stroma.Methodology and principal findingsFive candidate molecules identified by transcript profiling of developmental prostate mesenchyme were selected using a wholemount in situ hybridisation screen and studied Decorin (Dcn), Semaphorin6D (Sema6D), SPARC/Osteonectin (SPARC), Sprouty1 (Spry-1) and Tsukushi (Tsku). Expression in rat tissues was evaluated using wholemount in situ hybridisation (postnatal day (P) 0.5) and immunohistochemistry (embryonic day (E) E17.5, E19.5; P0.5; P6; 28 & adult). Four candidates (Decorin, SPARC, Spry-1, Tsukushi) were immunolocalised in human foetal prostate (weeks 14, 16, 19) and expression of Decorin was evaluated on a human prostate cancer tissue microarray. In embryonic and perinatal rats Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi were expressed with varying distribution patterns throughout the mesenchyme at E17.5, E19.5, P0.5 and P6.5. In P28 and adult prostates there was either a decrease in the expression (Semaphorin6D) or a switch to epithelial expression of SPARC, and Spry-1, whereas Decorin and Tsukushi were specific to mesenchyme/stroma at all ages. Expression of Decorin, SPARC, Spry-1 and Tsukushi in human foetal prostates paralleled that in rat. Decorin showed mesenchymal and stromal-specific expression at all ages and was further examined in prostate cancer, where stromal expression was significantly reduced compared with non-malignant prostate.Conclusion and significanceWe describe the spatio-temporal expression of Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi in developing prostate and observed similar mesenchymal expression patterns in rat and human. Additionally, Decorin showed reduced expression in prostate cancer stroma compared to non-malignant prostate stroma.

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Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies.

Publications

Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies.

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