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2015 ; 15
(ä): 761
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Oxalate induces breast cancer
#MMPMID26493452
Castellaro AM
; Tonda A
; Cejas HH
; Ferreyra H
; Caputto BL
; Pucci OA
; Gil GA
BMC Cancer
2015[Oct]; 15
(ä): 761
PMID26493452
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BACKGROUND: Microcalcifications can be the early and only presenting sign of
breast cancer. One shared characteristic of breast cancer is the appearance of
mammographic mammary microcalcifications that can routinely be used to detect
breast cancer in its initial stages, which is of key importance due to the
possibility that early detection allows the application of more conservative
therapies for a better patient outcome. The mechanism by which mammary
microcalcifications are formed is still largely unknown but breast cancers
presenting microcalcifications are more often associated with a poorer prognosis.
METHODS: We combined Capillary Electrochromatography, histology, and gene
expression (qRT-PCR) to analyze patient-matched normal breast tissue vs. breast
tumor. Potential carcinogenicity of oxalate was tested by its inoculation into
mice. All data were subjected to statistical analysis. RESULTS: To study the
biological significance of oxalates within the breast tumor microenvironment, we
measured oxalate concentration in both human breast tumor tissues and adjoining
non-pathological breast tissues. We found that all tested breast tumor tissues
contain a higher concentration of oxalates than their counterpart
non-pathological breast tissue. Moreover, it was established that oxalate induces
proliferation of breast cells and stimulates the expression of a pro-tumorigenic
gene c-fos. Furthermore, oxalate generates highly malignant and undifferentiated
tumors when it was injected into the mammary fatpad in female mice, but not when
injected into their back, indicating that oxalate does not induce cancer
formation in all types of tissues. Moreover, neither human kidney-epithelial
cells nor mouse fibroblast cells proliferate when are treated with oxalate.
CONCLUSIONS: We found that the chronic exposure of breast epithelial cells to
oxalate promotes the transformation of breast cells from normal to tumor cells,
inducing the expression of a proto-oncogen as c-fos and proliferation in breast
cancer cells. Furthermore, oxalate has a carcinogenic effect when injected into
the mammary fatpad in mice, generating highly malignant and undifferentiated
tumors with the characteristics of fibrosarcomas of the breast. As oxalates seem
to promote these differences, it is expected that a significant reduction in the
incidence of breast cancer tumors could be reached if it were possible to control
oxalate production or its carcinogenic activity.
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