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The Role of Hydrogen Peroxide as an Endogenous Growth Factor in Human Breast Cancer Cells
Author(s) -
Sen Suvajit,
Kawahara Brian,
Chaudhuri Gautam
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.543.7
Recently a significant number of studies have reported the role of ROS in the progression of a variety of cancers including breast cancer. In this study we have assessed the levels of O 2 − and H 2 O 2 in a panel of breast cancer cells comprising both estrogen receptor positive and negative cell lines and compared them with those of normal human breast epithelial cells. We have established a significant role of H 2 O 2 in breast cancer survival and proliferation by either silencing or overexpressing catalase in a breast cancer cell line, MDA‐MB‐468. We observed that silencing of catalase was accompanied by an increase in H 2 O 2 production accompanied by an increase in proliferation rate. This was associated with an increase in the phosphorylation status of ERK1/2 and AKT along with a decrease in PP2A (protein phosphatase 2A) activity. Conversely over expression of catalase in MDA‐MB‐468 caused a significant reduction in H 2 O 2 production resulting in apoptosis with a decrease in phosphorylation of ERK1/2 and AKT along with an increase in PP2A activity. This strongly indicated the role of H 2 O 2 as an endogenous growth factor in breast cancer cells. We further established this fact by obtaining similar results by overexpressing GPX1(glutathione peroxidase1) another H 2 O 2 scavenging enzyme. Interestingly overexpression of catalase did not result in apoptosis in normal human mammary epithelial cells attributing this phenomenon specifically to cancer cells, lending a significant therapeutic potential to the findings.