Mouse DMP-1 ELISA Kit

Our recent work has indicated that the DMP1 locus on 7q21, encoding a haplo-insufficient tumour suppressor, is hemizygously deleted at a high frequency in breast cancer. The locus encodes DMP1 protein, an activator of the p53 pathway leading to cell cycle arrest and senescence, and two other functionally undefined isoforms, DMP1 and DMP1. In this study, we show that the DMP1 locus is alternatively spliced in approximate to 30% of breast cancer cases with relatively decreased DMP1 and increased DMP1 expression. RNA-seq analyses of a publicly available database showed significantly increased DMP1mRNA in 43-55% of human breast cancers, dependent on histological subtypes. Similarly, DMP1 protein was found to be overexpressed in approximate to 60% of tumours relative to their surrounding normal tissue. Importantly, alteration of DMP1 splicing and DMP1 overexpression were associated with poor clinical outcomes of the breast cancer patients, indicating that DMP1 may have a biological function. Indeed, DMP1 increased proliferation of non-tumourigenic mammary epithelial cells and knockdown of endogenous DMP1 inhibited breast cancer cell growth. To determine DMP1's role in vivo, we established MMTV-DMP1 transgenic mouse lines. DMP1 overexpression was sufficient to induce mammary gland hyperplasia and multifocal tumour lesions in mice at 7-18 months of age. The tumours formed were adenosquamous carcinomas with evidence of transdifferentiation and keratinized deposits. Overall, we identify alternative splicing as a mechanism utilized by cancer cells to modulate the DMP1 locus through diminishing DMP1 tumour suppressor expression, while simultaneously up-regulating the tumour-promoting DMP1 isoform. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Notch is actively involved in various life processes including osteogenesis; however, the role of Notch signalling in the terminal mineralisation of bone is largely unknown. In this study, it was noted that Hey1, a downstream target of Notch signalling was highly expressed in mature osteocytes compared to osteoblasts, indicating a potential role of Notch in osteocytes. Using a recently developed thermosensitive cell line (IDG-SW3), we demonstrated that dentin matrix acidic phosphoprotein 1 (DMP1) expression was inhibited and mineralisation process was significantly altered when Notch pathway was inactivated via administration of N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch. Dysregulation of Notch in osteocyte differentiation can result in spontaneous deposition of calcium phosphate on collagen fibrils, disturbed transportation of intracellular mineral vesicles, alteration of mineral crystal structure, decreased bonding force between minerals and organic matrix, and suppression of dendrite development coupled with decreased expression of E11. In conclusion, the evidence presented here suggests that Notch plays a critical role in osteocyte differentiation and biomineralisation process.