"Oxalate Microcalcifications Induce Breast Cancer Tumors"

CASTELLARO AM, PUCCI O, TONDA A, CEJAS H, CAPUTTO BL, GIL GA.

Buenos Aires

Congreso; Molecular mechanisms in cell signaling and gene expression; 2013

Microcalcifications are routinely used to detect breast cancer in its early stages, these early detections gives for a better patient outcome. Mammary microcalcifications are mainly composed of calcium oxalate or calcium phosphate. Oxalate has been considered as an inert end product of the metabolism. However, its accumulation is thought to be toxic to living tissues. Exposure of renal epithelial cells to oxalate leads to diverse events as expression of immediate early genes (IEG), cell growth and up or down-regulation of more than 1000 genes. Herein, we have obtained good evidence supporting the hypothesis that the exposure of breast epithelial cells to excreted oxalate in a chronic way sets the stage for transformation from normal to fully developed breast tumors. Oxalate induced DNA synthesis and IEG over-expression in MCF7 and MDAMB231 human breast cancer cells in culture. Additionally, in human breast cancer tissues we found a strict correlation between oxalate concentration and overexpression of c-Fos and Fra-1. Surprisingly, female mice that were injected with oxalate periodically during a month generated very aggressive tumors a month later, after the treatment was finished. c-Fos and Fra-1 were also found over-expressed in these tumors. Furthermore, the final oxalate concentrations in the mice tumors were analogous to those found in the human breast tumor tissues.