Identification of a<i>DMBT1</i>polymorphism associated with increased breast cancer risk and decreased promoter activity

Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan; Schmutzhard, Julia; Strobel-Freidekind, Olga; Gronert-Sum, Sabine; Mietag, Carola; D’Amato, Mauro; Schlehe, B.; Hemminki, Kari; Sutter, Christian; Ditsch, Nina; Blackburn, Anneke C.; Hill, Linda Z.; Jerry, D. Joseph; Bugert, Peter; Weber, Bernhard H. F.; Niederacher, Dieter; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Schmutzler, Rita K.; Engel, Christoph; Meindl, Alfons; Bartram, Claus R.; Mollenhauer, Jan; Burwinkel, Barbara

doi:10.1002/humu.21134

Cited by 20 publications

(18 citation statements)

References 35 publications

(49 reference statements)

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“…Studies with mice have suggested that DMBT1/ gp340/SAG expression is related to breast cancer susceptibility, being significantly reduced in tumor compared with normal breast tissue (Blackburn et al, 2007). These results have been further confirmed by the identification of two polymorphisms associated with increased risk of breast cancer in women older than 60 years old (Tchatchou et al, 2010). It is noteworthy that one of the polymorphisms was located at the promoter region of the DMBT1 gene and was associated with a significantly reduced promoter activity in vitro.…”

Section: B Therapeutic and Diagnostic Potentialmentioning

confidence: 85%

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Moestrup²,

et al. 2011

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Section: B Therapeutic and Diagnostic Potentialmentioning

confidence: 85%

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

Moestrup²,

et al. 2011

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“…We noted a significant downregulation of Dmbt1 , a glycoprotein of the scavenger receptor cysteine-rich (SRCR) family, with roles in immunity and cancer (Mollenhauer et al 1997). Dmbt1 was identified as a modifier of susceptibility to mammary tumors in Trp53+/− BALB/c breast cancer model (Blackburn et al 2007), and Dmbt1 polymorphisms are associated with increased risk of breast cancer (Tchatchou et al 2010). …”

Section: Discussionmentioning

confidence: 99%

MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas

Huang

Anwar

et al. 2016

Oncogene

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Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly down regulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse. Ccn6fl/fl; MMTV-Cre mice displayed severe defects in ductal branching and abnormal age-related involution compared to littermate controls. Ccn6fl/fl ;MMTV-Cre mice developed invasive high grade mammary carcinomas with bona fide EMT, histologically similar to human metaplastic breast carcinomas. Global gene expression profiling of Ccn6fl/fl mammary carcinomas and comparison of orthologous genes with a human metaplastic carcinoma signature revealed a significant overlap of 87 genes (p=5×10−11). Among the shared deregulated genes between mouse and human are important regulators of epithelial morphogenesis including Cdh1, Ck19, Cldn3 and 4, Ddr1, and Wnt10a. These results document a causal role for Ccn6 deletion in the pathogenesis of metaplastic carcinomas with histological and molecular similarities with human disease. We provide a platform to study new targets in the diagnosis and treatment of human metaplastic carcinomas, and a new disease relevant model in which to test new treatment strategies.

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“…(13,26) To this end, DMBT1 was proposed as putative tumour suppressor gene for a variety of cancers like brain, (9,27) gastrointestinal, (12,28) breast (10,11,29,30) and lung cancer (31) ; albeit its role might be complex. Other studies showed that DMBT1 is also involved in the development of epithelia and in functions of the immune system.…”

Section: Discussionmentioning

confidence: 99%

Dmbt1 does not affect a Western style diet-induced liver damage in mice

Reichold

Brenner

Förster-Fromme

et al. 2013

J. Clin. Biochem. Nutr.

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In the last three decades the prevalence of non-alcoholic fatty liver disease has markedly increased. Results from epidemiologic studies indicate that not only a general overnutrition but rather a diet rich in sugar, fat and cholesterol (= Western style diet) maybe a risk factor for the development of non-alcoholic fatty liver disease. Concerning liver diseases, it is known that Deleted in malignant brain tumors 1 is amongst others related to liver injury and repair. In addition Deleted in malignant brain tumors 1 seems to play a role in regard to the maintenance of the intestinal homeostasis and the regulation of food intake. Starting from this background the aim of the present study was to investigate if Dmbt1 plays a role in Western style diet-induced non-alcoholic steatohepatitis in mice. Dmbt1+/+ and Dmbt1−/− mice were fed a Western style diet or control diet ad libitum for 12 weeks. Both Western style diet fed groups gained significant more weight than the controls and developed a mild non-alcoholic steatohepatitis. The presence/absence of functional Deleted in malignant brain tumors 1 had no effect on parameters like food intake, weight gain, fasting glucose, and liver damage. These results suggest that Deleted in malignant brain tumors 1 plays a minor part on the development of a diet-induced liver damage in mice.

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Identification of aDMBT1polymorphism associated with increased breast cancer risk and decreased promoter activity

Cited by 20 publications

References 35 publications

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

The Conserved Scavenger Receptor Cysteine-Rich Superfamily in Therapy and Diagnosis

MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas

Dmbt1 does not affect a Western style diet-induced liver damage in mice

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