Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells

Mina Yaar, Mark S. Eller, Izabela Panova, John Kubera, Lee Hng Wee, Kenneth H Cowan, Barbara A. Gilchrest

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Introduction: Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage response pathways. Methods: The human breast carcinoma cell line MCF-7, the adriamycin-resistant MCF-7 (Adr/MCF-7) cell line, as well as normal human mammary epithelial (NME) cells were treated with DNA oligonucleotides homologous to the telomere 3' overhang (T-oligos). SCID mice received intravenous injections of MCF-7 cells followed by intravenous administration of T-oligos. Results: Acting through ataxia telangiectasia mutated (ATM) and its downstream effectors, T-oligos induced apoptosis and senescence of MCF-7 cells but not NME cells, in which these signaling pathways were induced to a far lesser extent. In MCF-7 cells, experimental telomere loop disruption caused identical responses, consistent with the hypothesis that T-oligos act by mimicking telomere overhang exposure. In vivo, T-oligos greatly prolonged survival of SCID mice following intravenous injection of human breast carcinoma cells. Conclusion: By inducing DNA damage-like responses in MCF-7 cells, T-oligos provide insight into innate cancer avoidance mechanisms and may offer a novel approach to treatment of breast cancer and other malignancies.

Original languageEnglish (US)
Article numberR13
JournalBreast Cancer Research
Volume9
Issue number1
DOIs
StatePublished - Jan 26 2007

Fingerprint

MCF-7 Cells
Apoptosis
Breast Neoplasms
Telomere
DNA
SCID Mice
Intravenous Injections
DNA Damage
Neoplasms
Breast
Epithelial Cells
Cell Line
Ataxia Telangiectasia
Mutation Rate
Oligonucleotides
Intravenous Administration
Carcinogens
Doxorubicin
Cause of Death
Carcinogenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yaar, M., Eller, M. S., Panova, I., Kubera, J., Wee, L. H., Cowan, K. H., & Gilchrest, B. A. (2007). Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells. Breast Cancer Research, 9(1), [R13]. https://doi.org/10.1186/bcr1646

Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells. / Yaar, Mina; Eller, Mark S.; Panova, Izabela; Kubera, John; Wee, Lee Hng; Cowan, Kenneth H; Gilchrest, Barbara A.

In: Breast Cancer Research, Vol. 9, No. 1, R13, 26.01.2007.

Research output: Contribution to journalArticle

Yaar, M, Eller, MS, Panova, I, Kubera, J, Wee, LH, Cowan, KH & Gilchrest, BA 2007, 'Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells', Breast Cancer Research, vol. 9, no. 1, R13. https://doi.org/10.1186/bcr1646
Yaar, Mina ; Eller, Mark S. ; Panova, Izabela ; Kubera, John ; Wee, Lee Hng ; Cowan, Kenneth H ; Gilchrest, Barbara A. / Telomeric DNA induces apoptosis and senescence of human breast carcinoma cells. In: Breast Cancer Research. 2007 ; Vol. 9, No. 1.
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