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Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization

Qadir, M. A., Kwok, B., Dragowska, W. H., To, K. H., Le, D., Bally, M. B., Gorski, Sharon M.·2008·Breast Cancer Research and Treatment
DOI 10.1007/s10549-007-9873-4
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Abstract

Macroautophagy (autophagy), a process for lysosomal degradation of organelles and long-lived proteins, has been linked to various pathologies including cancer and to the cellular response to anticancer therapies. In the human estrogen receptor positive MCF7 breast adenocarcinoma cell line, treatment with the endocrine therapeutic tamoxifen was shown previously to induce cell cycle arrest, cell death, and autophagy. To investigate specifically the role of autophagy in tamoxifen treated breast cancer cell lines, we used a siRNA approach, targeting three different autophagy genes, Atg5, Beclin-1, and Atg7. We found that knockdown of autophagy, in combination with tamoxifen in MCF7 cells, results in decreased cell viability concomitant with increased mitochondrial-mediated apoptosis. The combination of autophagy knockdown and tamoxifen treatment similarly resulted in reduced cell viability in the breast cancer cell lines, estrogen receptor positive T-47D and tamoxifen-resistant MCF7-HER2. Together, these results indicate that autophagy has a primary pro-survival role following tamoxifen treatment, and suggest that autophagy knockdown may be useful in a combination therapy setting to sensitize breast cancer cells, including tamoxifen-resistant breast cancer cells, to tamoxifen therapy.

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Metadata

Authors
Qadir, M. A., Kwok, B., Dragowska, W. H., To, K. H., Le, D., Bally, M. B., & Gorski, S. M.
Venue
Breast Cancer Research and Treatment
Publisher
Springer Science and Business Media LLC
Published
2008-01-03
Volume
112
Issue
3
Pages
389-403
ISSN
  • 0167-6806
  • 1573-7217
DOI
10.1007/s10549-007-9873-4
Cited by
201
References
4
Language
en
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization. https://app.cochat.ai/papers/10.1007/s10549-007-9873-4
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Qadir, M. A., Kwok, B., Dragowska, W. H., To, K. H., Le, D., Bally, M. B., & Gorski, S. M. (2008). Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization. Breast Cancer Research and Treatment. https://doi.org/10.1007/s10549-007-9873-4