Article ; Online: Deposition of calcium in an in vitro model of human breast tumour calcification reveals functional role for ALP activity, altered expression of osteogenic genes and dysregulation of the TRPM7 ion channel.
2019 Volume 9, Issue 1, Page(s) 542
Abstract: ... analysis of calcium deposition, alkaline phosphatase (ALP) activity and changes in expression of key genes ... mineralising in vitro, MDA-MB-231 and SKBR3. Mineralising cell lines displayed higher levels of ALP activity ... mechanism by which they form remains incompletely understood. Following development of an in vitro model ...
| Abstract | Microcalcifications are vital mammographic indicators contributing to the early detection of up to 50% of non-palpable tumours and may also be valuable as prognostic markers. However, the precise mechanism by which they form remains incompletely understood. Following development of an in vitro model using human breast cancer cells lines cultured with a combination of mineralisation-promoting reagents, analysis of calcium deposition, alkaline phosphatase (ALP) activity and changes in expression of key genes was used to monitor the calcification process. Two cell lines were identified as successfully mineralising in vitro, MDA-MB-231 and SKBR3. Mineralising cell lines displayed higher levels of ALP activity that was further increased by addition of mineralisation promoting media. qPCR analysis revealed changes in expression of both pro- (RUNX2) and anti- (MGP, ENPP1) mineralisation genes. Mineralisation was suppressed by chelation of intracellular Ca |
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| MeSH term(s) | Alkaline Phosphatase/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Calcinosis/metabolism ; Calcium/metabolism ; Calcium-Binding Proteins/genetics ; Core Binding Factor Alpha 1 Subunit/genetics ; Extracellular Matrix Proteins/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; Magnesium/metabolism ; Models, Biological ; Osteogenesis/genetics ; Phosphoric Diester Hydrolases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Pyrophosphatases/genetics ; Real-Time Polymerase Chain Reaction ; TRPM Cation Channels/metabolism ; Matrix Gla Protein |
| Chemical Substances | Calcium-Binding Proteins ; Core Binding Factor Alpha 1 Subunit ; Extracellular Matrix Proteins ; RUNX2 protein, human ; TRPM Cation Channels ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Alkaline Phosphatase (EC 3.1.3.1) ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; ectonucleotide pyrophosphatase phosphodiesterase 1 (EC 3.1.4.1) ; Pyrophosphatases (EC 3.6.1.-) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP) |
| Language | English |
| Publishing date | 2019-01-24 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-018-36496-9 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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