Endonuclease G promotes cell death of non-invasive human breast cancer cells

Abstract

The invasiveness of breast cancer cells was shown to be associated with the suppressed ability to develop apoptosis. The role of cell death DNases/endonucleases has not been previously examined in relation with the invasiveness of breast cancer cells. We have compared the activity of the endonucleases in seven human breast cancer cell lines different in the level of invasiveness and differentiation. The invasiveness of cell lines was confirmed by an in vitro Matrigel-based assay. The total endonuclease activity in the differentiated non-invasive (WDNI) cell lines was higher than that in the poorly differentiated invasive (PDI) cells. The expression of EndoG strongly correlated with the degree of estrogen receptor expression and showed an inverse correlation with vimentin and matrix metalloproteinase-13. The EndoG-positive WDNI cells were more sensitive to etoposide-or camptothecin-induced cell death than EndoG-negative PDI cells. Silencing of EndoG caused inhibited of SK-BR-3 WDNI cell death induced by etoposide. Human ductal carcinomas in situ expressed high levels of EndoG, while invasive medullar and ductal carcinomas had significantly decreased expression of EndoG. This correlated with decreased apoptosis as measured by TUNEL assay. Our findings suggest that the presence of EndoG in non-invasive breast cancer cells determines their sensitivity to apoptosis, which may be taken into consideration for developing the chemotherapeutic strategy for cancer treatment.

Reactive oxygen species‐dependent EndoG release mediates cisplatin‐induced caspase‐independent apoptosis in human head and neck squamous carcinoma cells

“…EndoG and AIF have been reported to be caspase-independent death effectors 16,17 and play important roles in caspaseindependent apoptosis of osteosarcoma, 43 multiple myeloma 44 and breast cancer cells. 45 Until now, only AIF has been reported to be involved in caspase-independent apoptosis induced by cisplatin. 19,30 AIF was detected from other HNSCC cells, HN3, (data not shown) which is sensitive to cisplatin treatment, 26,32 and it is possible that AIF plays roles in caspase-independent apoptosis in cisplatin-treated HN3 cells.…”

Hypoxia-induced human endonuclease G expression suppresses tumor growth in a xenograft model

“…hEndoG has been shown to digest both single strand RNA as well as DNA and functions during apoptosis. [14][15][16][17][18][19] It is normally sequestered between the inner and outer membranes of the mitochondria and is released with other apoptotic factors during apoptosis. In addition, we have incorporated a TLM 21 into the N-terminus of our chimeric protein to provide a possible bystander capability that can be tested in future applications.…”

“…14 Human endonuclease G is normally compartmentalized in the mitochondria and following its release into the cytoplasm, it can function in apoptotic processes. [15][16][17][18][19] The expression of this novel protein construct has been placed under the control of a conditional promoter, which consists of five HREs in tandem upstream of a minimal cytomegalovirus promoter. 20 In addition, we fused the coding sequence of the mature hEndoG (without the mitochondrial localization signal) to the coding sequence of the ODD domain of HIF-1a.…”

Cisplatin-induced apoptotic endonuclease EndoG inhibits telomerase activity and causes malignant transformation of human CD4+ T lymphocytes

“…Обратную транскрипцию (ОТ) и ПЦР в реальном времени проводили по методике, описанной Basnakian с совт. [19]. Для этого 5 мкг тотальной РНК подвергали реакции ОТ в 25 мкл реакционной смеси ("Invitrogen") по протоколу компании-производителя.…”