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

Alexei G. Basnakian, Eugene O. Apostolov, Xiaoyan Yin, Stanley O. Abiri, Anna G. Stewart, Amar B. Singh, Sudhir V. Shah

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4139-4149
Number of pages11
JournalExperimental Cell Research
Volume312
Issue number20
DOIs
StatePublished - Dec 10 2006

Keywords

  • Apoptosis
  • Breast cancer
  • Chemotherapy
  • DNase I
  • Differentiation
  • Invasiveness

ASJC Scopus subject areas

  • Cell Biology

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    Basnakian, A. G., Apostolov, E. O., Yin, X., Abiri, S. O., Stewart, A. G., Singh, A. B., & Shah, S. V. (2006). Endonuclease G promotes cell death of non-invasive human breast cancer cells. Experimental Cell Research, 312(20), 4139-4149. https://doi.org/10.1016/j.yexcr.2006.09.012