Endonuclease G promotes cell death of non-invasive human breast cancer cells.
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.
Basnakian
Alexei G
AG
Division of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences, slot #501, 4301 W. Markham St., Little Rock, AR 72205, USA. basnakianalexeig@uams.edu
Apostolov
Eugene O
EO
Yin
Xiaoyan
X
Abiri
Stanley O
SO
Stewart
Anna G
AG
Singh
Amar B
AB
Shah
Sudhir V
SV
D000818:Animals; D017209:Apoptosis; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002166:Camptothecin / Q000494:pharmacology; D016923:Cell Death; D045744:Cell Line, Tumor; D002465:Cell Movement; D053938:DNA Fragmentation; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D014162:Transfection
D005047:Etoposide; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D002166:Camptothecin