Abstract
Breast cancer is frequently characterized by calcifications in mammography. The mechanism for calcifications in breast cancer is not completely known. Understanding this mechanism will improve diagnostic accuracy. Herein, we demonstrated that calcifications occur and that alkaline phosphatase enzyme activity increases in MDA-MB-231 cells cultured using an osteogenic cocktail-containing medium. Microarray transcript analysis showed that the PI3K-Akt signaling pathway was significantly involved, with recruitment of placental alkaline phosphatase. Calcifications and alkaline phosphatase enzyme activity were suppressed by silencing placental alkaline phosphatase using a small interfering RNA. Inhibition of the PI3K-Akt signaling pathway suppressed phospho-c-Jun and placental alkaline phosphatase and resulted in absence of calcifications. These findings reveal that breast cancer cells acquire alkaline phosphatase enzyme activity via placental alkaline phosphatase expression and suggest that breast calcification formation is closely associated with the PI3K-Akt signaling pathway.
Highlights
Breast cancer is frequently characterized by calcifications in mammography
By a comprehensive analysis of transcription compared with osteoblastic cell line MC3T3-E1 in a microarray, we showed that placental alkaline phosphatase (PLAP) is involved in producing calcifications through PI3K-Akt signaling pathways
Human breast cancer cell lines MDA-MB-231and MDA-MB-468 and mouse preosteoblast cell line MC3T3-E1 were cultured in medium containing an osteogenic cocktail (OC)
Summary
Breast cancer is frequently characterized by calcifications in mammography. The mechanism for calcifications in breast cancer is not completely known. Inhibition of the PI3K-Akt signaling pathway suppressed phospho-c-Jun and placental alkaline phosphatase and resulted in absence of calcifications. In cases in which it is difficult to distinguish benign from malignant calcifications based on morphology and distribution, additional investigations such as biopsy or magnetic resonance imaging are required. This limits the ability to make a diagnosis based on calcifications alone. By a comprehensive analysis of transcription compared with osteoblastic cell line MC3T3-E1 in a microarray, we showed that placental alkaline phosphatase (PLAP) is involved in producing calcifications through PI3K-Akt signaling pathways
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