• PARK7 is associated with ER-positive breast cancer • PARK7 is a marker for favorable prognosis in ductal breast cancer • PARK7 is not involved in resistance to aldehyde stress In cancer, aerobic glycolysis predominantly used to provide energy. This high glycolytic flow results in the formation of reactive aldehydes such as glyoxal and methylglyoxal forming advanced glycation end products (AGEs) by reacting with free amino groups on proteins, nucleic acids and lipids. AGE-modification inhibits enzymes and signaling molecules, stiffens the extracellular matrix and promotes inflammation via the receptor for AGEs (RAGE). Tumor cells activate specific defense systems such as glyoxalase-I (GLO-1) to prevent high accumulation of AGEs. Parkinson-disease protein 7 PARK7 (DJ-1) catalyzes the removal of early glycation adducts. It is therefore likely involved in the defense against AGE accumulation. We investigated the prognostic impact of PARK7 in a retrospective breast cancer cohort by immunohistochemistry. PARK7 correlated positively with estrogen receptor status, accumulation of the AGE carboxymethyl-lysin but not GLO-1 expression, which was consistent with mRNA data from the METABRIC study. PARK7 expression indictaed favorable relapse free survival in invasive ductal breast cancer. PARK7 protein and mRNA were determined in five breast cancer cell lines under basal conditions and under aldehyde stress. None of the cell-lines responded to aldehyde stress by significant changes in PARK7 expression. Down-regulation of PARK7 in MCF-7 by small interfering RNA did not alter sensitivity towards glyoxal. In conclusion, PARK7 protein expression was associated with AGE accumulation and favorable prognosis in ductal breast cancer suggesting a possible application as biomarker. Further research is needed to understand the molecular mechanisms of gene regulation and function of the PARK7 protein in breast cancer.
Nass et al. (Sun,) studied this question.